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Scopolamine Effects Under a Titrating-Delayed-Nonmatching-to-Position Procedure

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In a study of working memory, the performance of rats under titrating-delayednonmatching- to-position (TDNMTP) procedures was examined. Overall accuracy and the number of trials completed were inversely related to titration value, whereas the highest delay attained was directly related to titration value. When given intraperitoneally, scopolamine significantly reduced the highest delay attained without significantly affecting other performance measures for most administrations. Subcutaneous administrations significantly reduced all performance measures, suggesting that, as in most prior studies, the drug’s disruptive effects were not limited to memory processes. These findings demonstrate the feasibility of using TDNMTP procedures with rats, but further research is necessary to determine if such procedures are especially valuable in studying working memory and drug effects thereon.
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scoPolaMiNe eFFecTs UNdeR a TiTRaTiNg-delayed-
NoNMaTchiNg-To-PosiTioN PRocedURe

Western Michigan University
In a study of working memory, the performance of rats under titrating-delayed-
nonmatching-to-position (TDNMTP) procedures was examined. Overall accura-
cy and the number of trials completed were inversely related to titration value,
whereas the highest delay attained was directly related to titration value. When
given intraperitoneally, scopolamine significantly reduced the highest delay
attained without significantly affecting other performance measures for most
administrations. Subcutaneous administrations significantly reduced all perfor-
mance measures, suggesting that, as in most prior studies, the drug’s disruptive
effects were not limited to memory processes. These findings demonstrate the
feasibility of using TDNMTP procedures with rats, but further research is neces-
sary to determine if such procedures are especially valuable in studying working
memory and dr ug effects thereon.
    
        

   
               


     
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


      



          
 
         
       
                      



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        
       
        
             
      


 


        
     
              






      

         

        



      

 
    
           


    
            


   
            
         
         
           
             




       
        
               
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

       
    

          

                
           
     
              

          

     




  
         
        
              


   
   
       
        

       


            


  
  
    
  
           
              



Subjects
        
 

40

         
       
×× 

   

           

Guide for the Care and Use of Laboratory Animals

Apparatus
       
     ×    ×     
     
     

       

       



        


Behavioral Procedure
 
    
                  

 

               




              

   


                
              

           
41

  
             

             


     






Pharmacological Procedure


  

         
  
   

  
            
  


         
        
                  





Data Analysis
         
          


              
p

              
          
  

42
    




    
       


×Fp
F
       

   
 
   
   
      
        
   F   
p

      
     
   

    

    
    
     
   
      
     
   
    
     
   
        
  F   
pF
p
       
    F
   p     

    
     

       
    
Figure 1. Mean (± standard error of
mean) overall accuracy (percentage of
correct responses), number of trials
completed, and highest delay reached
by 7 rats during baseline (no injection)
and vehicle-control sessions. Rats were
exposed to four variations of a TDNMTP
procedure, with the variations defined
in terms of the length of the titration
interval, which is indicated.
Titration Value
43


   

   
    



  
    
   
    
   




  
Fp
F  p 
    
   
Fp
    

    
    
    



     
    
  
    
   
  F   
p      
F p  
  
  
  F
p



  




Figure 2. Ef fects of scopolamine on overall
accuracy, trials completed, and highest delay
reached. Data during sessions in which the
indicated dose of drug was given are expressed
as a percentage of vehicle control (see Figure 1).
All doses were given intraperitoneally (IP) except
for the indicated .06 mg/kg subcutaneous (SC)
dose. Asterisks indicate doses where the drug
mean differed significantly (p < .05) from the
vehicle-control mean.

44
              
  
     



Figure 3. Effect sizes (Cohen’s D) for the highest delay reached, by dose of scopolamine.
Data are presented separately for each of the four titration values. IP = intraperitoneal;
SC = subcutaneous.
    





         
             
                
            
            
       
                
            
     
                 
           
   

       
       
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





               

           
               







         


      
      


        





         


         
       
            



   
       

          






   
           


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 
 
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      
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           
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          
         
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


 
        


          
x
y       
          
         
       


 


47

        
 




Figure 4. Mean values for the highest delay reached when the 0.06 mg/kg subcutaneous
(SC) dose of scopolamine was administered and in the immediately prior vehicle-control
sessions when the same number of trials are considered. Data are presented for each
of the four titration values.
           
        









            
              


 

         
      
        
      





Psychopharmacology

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



Psychopharmacology





Journal of
Pharmacology and Experimental Therapeutics



Psychopharmacology
 



European Journal of Pharmacology



Behavioural Brain Research
 


European
Journal of Neuroscience


Behavioural Brain
Research
  



Proceedings of the National Academy
of Sciences of the United States of America


Guide for the care
and use of laboratory animals



Pharmacology Biochemistr y and Behavior



Progress in
Neuro-Psychopharmacology and Biological Psychiatry



Journal of Pharmacological
and Toxicological Methods




Neurotoxicology and
Teratology


49


Journal of the Experimental Analysis of Behavior




Journal of Pharmacology and Experimental Therapeutics



Introduction to behavioral pharmacology




Behavioural Processes






Behavioural Pharmacology




Brain Research



Behavioural Brain Research




Psychopharmacology



Psychopharmacology



Journal of Pharmacology and Experimental Therapeutics

 


Journal of Experimental Psychology: Animal Behavior
Processes




Behavioral Neuroscience



American Journal of Mental
Deficiency
... One rat from each pair was randomly assigned to the WMT group; the other rat was assigned to the sham-training group. WMT was a variation of the titrating-delay match-to-position (TDMTP) task, a commonly used operant preparation to assess working memory in nonhumans (see Kangas, Vaidya, & Branch, 2010;Porritt & Poling, 2008). We selected this task for two reasons. ...
... Working-memory training (WMT). Rats assigned to the WMT group completed 140 WMT sessions in which they earned food by making correct choices in a modified TDMTP task (see, e.g., Kangas et al., 2010;Porritt & Poling, 2008). In this procedure, rats were required to remember a cue over a delay period (i.e., retention interval) in which the cue was absent. ...
... First, it is possible that the working-memory ability of the WMT rats did not improve (relative to the shamtrained rats) by the working-memory training that was provided. One piece of evidence against this is that the posttraining retention intervals across which our rats remembered the sample stimulus are, to the best or our knowledge, the highest reported in the titrating-delay match-toposition literature (e.g., Porritt & Poling, 2008, using a similar procedure, reported a mean peak retention interval of 32.85 s, SEM ¼ 4.56, whereas our WMT rats achieved a mean peak retention interval of 68.32 s, SEM ¼ 5.71, in the posttraining reassessment of working memory). More robust evidence that WMT positively impacted working-memory ability would have been obtained had WMT rats performed better than Sham rats in a novel working-memory task (for review of rodent working-memory preparations, see Dudchenko, 2004;Pontecorvo, Sahgal, & Steckler, 1996) and future studies might include such a posttraining test phase. ...
Article
Delay discounting describes the devaluation of a reward as the delay to the receipt of the reward increases. Because steep delay discounting is robustly correlated with a number of behavioral problems (e.g., substance dependence, gambling) and some evidence suggests steep discounting precedes and predicts drug-taking in humans and rats, this study sought to experimentally reduce rats' delay discounting. Human stimulant-dependent participants given working-memory training reportedly decreased their rates of discounting relative to a sham-training group (Bickel, Yi, Landes, Hill, & Baxter, 2011). To evaluate the cross-species generality of this effect, 38 male Long-Evans rats, matched on pretraining delay-discounting rates, were randomly assigned to receive 140 sessions of working-memory training or sham training (which required no memory of the sample stimulus). Large between-group differences in working memory were observed after training; however, posttraining delay-discounting rates were undifferentiated across groups. Potential explanations for these findings are discussed.
... Late responses corresponded to approximately 5% of all lever presses. This time (at least 2.5 s post stimulus offset) is within the range of animal models of working memory (Wallace et al., 1980;Porritt and Poling, 2008;Lind et al., 2015). Along with this, when we looked at the totality of responses, we could see that ITI responses after the reward window were distributed between 5 and 8 s. ...
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The ability to perceive the world is not merely a passive process but depends on sensorimotor loops and interactions that guide and actively bias our sensory systems. Understanding which and how cognitive processes participate in this active sensing is still an open question. In this context, the auditory system presents itself as an attractive model for this purpose as it features an efferent control network that projects from the cortex to subcortical nuclei and even to the sensory epithelium itself. This efferent system can regulate the cochlear amplifier sensitivity through medial olivocochlear (MOC) neurons located in the brainstem. The ability to suppress irrelevant sounds during selective attention to visual stimuli is one of the functions that have been attributed to this system. MOC neurons are also directly activated by sounds through a brainstem reflex circuit, a response linked to the ability to suppress auditory stimuli during visual attention. Human studies have suggested that MOC neurons are also recruited by other cognitive functions, such as working memory and predictability. The aim of this research was to explore whether cognitive processes related to delayed responses in a visual discrimination task were associated with MOC function. In this behavioral condition, chinchillas held their responses for more than 2.5 s after visual stimulus offset, with and without auditory distractors, and the accuracy of these responses was correlated with the magnitude of the MOC reflex. We found that the animals’ performance decreased in presence of auditory distractors and that the results observed in MOC reflex could predict this performance. The individual MOC strength correlated with behavioral performance during delayed responses with auditory distractors, but not without them. These results in chinchillas, suggest that MOC neurons are also recruited by other cognitive functions, such as working memory.
... Relações de identidade de cor ou forma, ou seja, a escolha definida como correta é a do estímulo de comparação com cor ou forma igual a do modelo, foram requeridas em 13 dos 21 experimentos. Dois estudos (Porritt & Poling, 2008;Robinson, Scheff, Pierre-Louis, & Han, 2000) utilizaram tarefas de escolha da posição diferente (oddity ou non matching) e três o MTS arbitrário. Neste último, o modelo e o estímulo de comparação correspondente não apresentam semelhança física; a relação é definida pelo experimentador (e.g., uma forma abstrata e um som). ...
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Titrating Delayed Matching-to-Sample (TDMTS) is used to investigate working memory and correlates. In this procedure, response that matches the sample is emitted after a time interval since the sample withdrawal (delay). Delay is adjusted based on correct and incorrect responses. The present paper presents a literature review of studies that manipulated methodological variables of TDMTS. From search in data bases, internet and references of the papers, 16 articles published from 1965 to 2019, that describe 21 experiments, were analyzed. This review showed the most used criteria and parameters values in the literature and summarized the effects of methodological aspects manipulated in studies. Longer adjusted delays were found to be related to: larger response ratios on sample; initial session delay setting based on previous session last values; more tolerant adjusting criteria; larger step sizes; and programming differential reinforcement for each discrimination. Those results call for controlled replications to assess generality, considering the variety of parameters, criteria and experimental subjects.
... Despite the occasional reduction in retention intervals, by session 65 of the working-memory task, all rats' accurate choices led to substantial increases in the retention interval relative to what was observed in the first 10 sessions of training. Indeed, the terminal retention intervals in our study are substantially longer than those produced by comparable procedures in animals given fewer sessions [41,46,47]. Thus, the TDMTP procedure used here might be a good choice for future studies evaluating the effects of working-memory training on subsequent delay discounting in rats. ...
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A number of maladaptive behaviors and poor health outcomes (e.g., substance abuse, obesity) correlate with impulsive choice, which describes the tendency to prefer smaller, immediate rewards in lieu of larger, delayed rewards. Working memory deficits are often reported in those diagnosed with the same maladaptive behaviors. Human studies suggest that impulsive choice is associated with working memory ability but, to date, only one study has explored the association between working memory and impulsive choice in rats and no relation was reported. The current study reevaluated the association between working memory and impulsive choice in 19 male Long-Evans rats. Psychophysical adjusting procedures were used to quantify working memory (titrating-delay match-to-position procedure) and impulsive choice (adjusting delay procedure). Rats were partitioned into low- and high-impulsive groups based on performance in the impulsive choice task. Low-impulsive rats performed significantly better in the working memory assessment. Across all rats, impulsive choice was negatively correlated with working memory performance. These findings support the hypothesis that prefrontal cortex function, specifically, working memory, is related to impulsive choice. Future research might profitably examine the experimental variables designed to influence working memory to evaluate the effects of these variables on impulsive choice and maladaptive behaviors with which it is correlated.
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We performed a meta-analysis of over 90 data sets from delayed matching-to-sample (DMTS) studies with 25 species (birds, mammals, and bees). In DMTS, a sample stimulus is first presented and then removed. After a delay, two (or more) comparison stimuli are presented, and the subject is rewarded for choosing the one matching the sample. We used data on performance vs. delay length to estimate two parameters informative of working memory abilities: the maximum performance possible with no delay (comparison stimuli presented as soon as the sample is removed), and the rate of performance decay as the delay is lengthened (related to memory span). We conclude that there is little evidence that zero-delay performance varies between these species. There is evidence that pigeons do not perform as well as mammals at longer delay intervals. Pigeons, however, are the only extensively studied bird, and we cannot exclude that other birds may be able to bridge as long a delay as mammals. Extensive training may improve memory, although the data are open to other interpretations. Overall, DMTS studies suggest memory spans ranging from a few seconds to several minutes. We suggest that observations of animals exhibiting much longer memory spans (days to months) can be explained in terms of specialized memory systems that deal with specific, biologically significant information, such as food caches. Events that do not trigger these systems, on the other hand, appear to be remembered for only a short time. Copyright © 2014 Elsevier B.V. All rights reserved.
Article
Behavioral paradigms applicable for use in both human and nonhuman subjects for investigating aspects of working/short-term memory are presented with a view towards exploring their strengths, weaknesses, and utility in a variety of experimental situations. Such procedures can be useful in teasing out specific aspects of mnemonic processes including discrimination, encoding, and retention. Delayed matching-to-position, delayed matching-to-sample (DMTS), and titrating matching-to-sample procedures are highlighted. Additionally, the application of DMTS tasks in preclinical and clinical settings is presented: drug effects on memory processes can be explored preclinically in animal models; normative data have been developed in human populations where they have been used in adults to explore the relationships between mnemonic processes and specific clinical entities such as Parkinsonism, senile dementia of the Alzheimer’s type, schizophrenia, and depression. Studies in children indicate that encoding and retention processes improve rapidly in the early years, plateauing prior to puberty. Noninvasive imaging techniques such as positron emission tomography (PET) indicate that activity in specific brain areas is associated with DMTS task performance and may serve to confirm roles for such structures in mnemonic processes. Published by Elsevier Science Inc.
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The differential outcomes effect refers to the increase in speed of acquisition or terminal accuracy that occurs in discrimination training when each of two or more discriminative stimuli is correlated with a different outcome (e.g. type of reinforcer). The present study demonstrated this effect in domestic hens exposed to a titrating-delayed-matching-to-sample procedure, under which correct responses increased (and incorrect responses decreased) the delay between the offset of a sample stimulus and the onset of two comparison stimuli. Colors of key illumination (red, green) were used as sample and comparison stimuli and correct responses resulted in 1- or 4-s food deliveries. When 1-s food deliveries consistently followed correct responses to one key color and 4-s food deliveries followed correct responses to the other key color, the maximum delay reached by the hens and their overall accuracy was significantly higher than when 1- and 4-s food deliveries were randomly arranged following correct responses to both key colors. These data constitute the first demonstration of the differential outcomes effect in chickens, and in any species evaluated under a titrating-delayed-matching-to-sample procedure.
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Behavioral paradigms applicable for use in both human and nonhuman subjects for investigating aspects of working/short-term memory are presented with a view towards exploring their strengths, weaknesses, and utility in a variety of experimental situations. Such procedures can be useful in teasing out specific aspects of mnemonic processes including discrimination, encoding, and retention. Delayed matching-to-position, delayed matching-to-sample (DMTS), and titrating matching-to-sample procedures are highlighted. Additionally, the application of DMTS tasks in preclinical and clinical settings is presented: drug effects on memory processes can be explored preclinically in animal models; normative data have been developed in human populations where they have been used in adults to explore the relationships between mnemonic processes and specific clinical entities such as Parkinsonism, senile dementia of the Alzheimer’s type, schizophrenia, and depression. Studies in children indicate that encoding and retention processes improve rapidly in the early years, plateauing prior to puberty. Noninvasive imaging techniques such as positron emission tomography (PET) indicate that activity in specific brain areas is associated with DMTS task performance and may serve to confirm roles for such structures in mnemonic processes. Published by Elsevier Science Inc.
Article
Five adult, male White Carneaux pigeons were trained to respond under a titrating delayed matching-to-sample schedule of reinforcement. Under this schedule, the length of the delay was changed as a function of the pigeons' performances in a manner that resulted in approximately 80% accuracy in matching performance. During the first five trials of each session, the delay value was fixed at either 3 sec or 30 sec (starting delay). On the 6th and all subsequent trials, the length of the delay value was increased by a fixed amount (the titration step), did not change or was decreased by an amount equal to the titration step. Initially, the starting delay and the titration step were set at 3 sec. These values were then systematically changed to a starting delay of 30 and a titration step of 3, and finally, a starting delay of 3 and a titration step of 1. Using this procedure, the effects of pentobarbital (0.3-10 mg/kg), cocaine (0.01-10 mg/kg), d-amphetamine (0.003-3 mg/kg) and phencyclidine (0.03-3 mg/kg) were determined under the different titration parameters. Pentobarbital was shown to decrease matching performance at doses (3, 5.6 and 10 mg/kg) that did not decrease response rates. Phencyclidine produced a similar effect at a dose of 1 mg/kg under two of the three phases of the experiment. No such specific effects were observed with cocaine or d-amphetamine. Thus, of the four drugs studied, pentobarbital showed the most pronounced effect on matching performance. Whether this represents merely a loss of stimulus control or a specific effect on memory is yet to be determined. In addition, the results of these experiments clearly show that when the delay value is allowed to change as a function of the pigeons' performance, pigeons are able to perform at or above 80% accuracy at longer delay values than those generally reported using fixed-delay values.