Western Michigan University ScholarWorks at WMU Dissertations Graduate College 4-1984 Effects of Anticonvulsant Drugs on Learning and Memory Mitchell Jon Picker Western Michigan University Follow this and additional works at: https://scholarworks.wmich.edu/dissertations Part of the Experimental Analysis of Behavior Commons Recommended Citation Picker, Mitchell Jon, "Effects of Anticonvulsant Drugs on Learning and Memory" (1984). Dissertations. 2416. https://scholarworks.wmich.edu/dissertations/2416 This Dissertation-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Dissertations by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. EFFECTS OF ANTICONVULSANT DRUGS ON LEARNING AND MEMORY by Mitchell Jon Picker A Dissertation Submitted to the Faculty of The Graduate College in partial fulfillment of the requirements of the Degree of Doctor of Philosophy Department of Psychology Western Michigan University Kalamazoo, Michigan April 1984 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. EFFECTS OF ANTICONVULSANT DRUGS ON LEARNING AND MEMORY Mitchell Jon Picker, Ph.D. Western Michigan University, 1984 The effects of phenobarbital, clonazepam, valproic acid, phenytoin, and ethosuximide were examined in pigeons performing under repeated ac­ quisition of response chains and delayed matching-to-sample procedures. In experiment I, clonazepam, valproic acid, ethosuximide, and phenytoin produced generally dose-dependent decreases in rate of responding, while phenobarbital had little consistent effect on response rate across the dose range studied. Phenobarbital and clonazepam produced dose-dependent increases in error rates (i.e., learning impairment). Although valproic acid and phenytoin generally increased error rates relative to control values, this effect was not directly dose-dependent or consistent across subjects. In contrast to the other anticonvulsants examined, ethosuxi­ mide had little effect on error rates. In experiment II, clonazepam, valproic acid, phenytoin, and ethosuximide reduced rates of responding to the sample stimulus as the dose was increased, while phenobarbital increased rates of responding at high doses. Phenobarbital, clonazepam, and valproic acid produced generally dose-dependent decreases in accuracy (i.e., memory impairment); ethosuximide and phenytoin failed to do so. These results suggest that there are qualitative as well as quantitative differences in the effects of anticonvulsant drugs under the repeated acquisition of response chains and delayed matching-to-sample procedures. with permission of the copyright owner. Further reproduction prohibited without permission. INFORMATION TO USERS This reproduction was made from a copy of a document sent to us for microfilming. While the most advanced technology has been used to photograph and reproduce this document, the quality of the reproduction is heavily dependent upon the quality of the material submitted. The following explanation of techniques is provided to help clarify markings or notations which may appear on this reproduction. 1. The sign or “target” for pages apparently lacking from the document photographed is “Missing Page(s)”. If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. 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Other_______________________________________________________ _________ University Microfilms International Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGEMENTS Sincere appreciation is extended to the individuals and pharma­ ceutical firms that provided the drugs and materials used in the pre­ sent series of experiments. Special thanks go to Scott Wallace who magically transformed many of these drugs into forms suitable for a preparation as an injection. My gratitude and thanks to Earl Johnson and the members of the Behavioral Pharmacology Laboratory for comments on an earlier version of this manuscript, Wesley White for his assistance in data collection, and members of my doctoral committee for their critical review of this work and helpful suggestions. I also wish to thank Alan Poling, my advisor, mentor, and friend, for his assistance throughout the duration of my graduate studies. I hope this dissertation adequately reflects his competence as a teacher / researcher / scientist, and his ability to mold a tabula rasa into a Behavioral Pharmacologist. In addition, I would like to thank Karen Doran for her assistance in the preparation of this manuscript, and for seven years of patience, love, devotion, and the impetus to obtain the degree of Doctor of Philosophy. Mitchell Jon Picker Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS ACKNOWLEDGEMENTS ................................ ii LIST OF FIGURES ................................ iv INTRODUCTION ................................ 1 Historical Background ................... 2 Behavioral Actions of Anticonvulsant Drugs 5 Pharmacology .............................. 11 EXPERIMENT I ................................ 27 Method ................................ 27 Results ................................ 32 Discussion ................................ 43 EXPERIMENT II ................................ 50 Method . 50 52 Results ................................ Discussion ................................ 65 69 GENERAL DISCUSSION .............................. 70 BIBLIOGRAPHY ................................ Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST OF FIGURES f i g u r e p a g e 1. Effects of phenobarbital on response rate and percent errors for individual subjects............................. 34 2. Effects of clonazepam on response rate and percent errors for individual subjects............................. 37 3. Effects of valproic acid on response rate and percent errors for individual subjects............................. 39 4. Effects of ethosuximide on response rate and percent errors for individual subjects............................. 42 5. Effects of phenytoin on response rate and percent errors for individual subjects............................. 45 6. Effects of phenobarbital on percent correct responses and rate of responding to the sample st i m u l u s ............ 55 7. Effects of clonazepam on