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INFORMATION to USERS the Most Advanced Technology Has Been INFORMATION TO USERS The most advanced technology has been used to photo­ graph and reproduce this manuscript from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. 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University Microfilms International A Bell & Howell Information Com pany 300 North Z eeb Road, Ann Arbor, Ml 48106-1346 USA 313/761-4700 800/521-0600 Order Number 9002021 The role of excitatory amino acids in the nucleus accumbens and subpallidal region in goal-directed locomotor activity Shreve, Paul Edward, Ph.D. The Ohio State University, 1989 UMI 300 N. ZeebRd. Ann Arbor, MI 48106 THE ROLE OF EXCITATORY AMINO ACIDS IN THE NUCLEUS ACCUMBENS AND SUBPALLIDAL REGION IN GOAL DIRECTED LOCOMOTOR ACTIVITY DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Paul E. Shreve, B.S., R.Ph. ***** The Ohio State University 1989 Reading Committee: Approved by: Dr. Norman J. Uretsky Dr. Allan M. Burkman Dr. Dennis B. McKay Adviser & College of Pharmacy Dr. Lane J. Wallace DEDICATION To my wife Sheila, I have so much to thank you for, and yet, words can not begin to express how much you mean to me. You are more than my loving wife, you are also my best friend whom I can confide in and draw strength from. You have always been there when I needed love and support. You encouraged and enabled me to achieve one of my major gc'ls in life. I am eternally grateful and indebted. Therefore, as an expression of my immeassurable love for you, I dedicate this dissertation to you. 11 ACKNOWLEDGEMENTS I wish to express my sincere appreciation to: Dr. Norman J. Uretsky for his support, instruction, and guidance throughout my years as a graduate student. I feel priviledged to have worked with such a skilled and knowledgeable scientist. His confidence in me has enabled my graduate career to be a productive endeavor. His friendship and sincere interest in me has made my life as a graduate student an enjoyable experience which I will always remember. Drs. Burkman, McKay, and Wallace for their constructive criticism of my work and suggestions in the preparation of this dissertation. 111 VITA September 23, 1959....................... Born - Pomeroy, Ohio, U.S.A. 1982....................................................... B.S. in Pharmacy, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 1983-1985............................................ Graduate Teaching Associate The Ohio State University Columbus, Ohio 1986-1989............................................ Graduate Research Associate The Ohio State University Columbus, Ohio HONORS 1982....................................................... Eli Lilly Achievement Award 1981....................................................... Rho Chi Honor Society 1981....................................................... Presented paper at Morgantown Undergraduate Research Seminars Morgantown, West Virginia 1988....................................................... ASPET Travel Award PUBLICATIONS Kolta, M., P. Shreve, and N.J. Uretsky (1985) Effect of methyl- phenidate pretreatment on the behavioral and biochemical responses to amphetmaine. Eur. J. of Pharmacol. 117:279-282. Kolta, M.G., P. Shreve, V. De Souza, and N.J. Uretsky (1985) Time course of development of the enhanced behavioral and bio­ chemical response to amphetamine after amphetamine pretreatment. Neuropharmacology 24:823-829. Shreve, P.E. and N.J. Uretsky (1988) Role of quisqualic acid receptors in the hypermotility response produced by the injection of AMPA Into the nucleus accumbens. Pharmacol. Biochem. & Behav. 30:379-384. iv Shreve, P.E. and N.J Uretsky (1988) Effect of GABAergic trans­ mission 1n the subpallidum on the hypermotility response to to Intraaccumbens administration of excitatory amino acids and plcrotoxin. Neuropharmacology 27:1271-1278. Kolta, M.G., P.E. Shreve, and N.J. Uretsky (1989) Effect of pretreatment with amphetamine on the Interaction between amphetamine and dopamine neurons 1n the nucleus accumbens. Neuropharmacology 28:9-14. Shreve, P.E. and N.J. Uretsky (1989) AMPA, kalnic acid, and N-methyl-D-aspart1c acid stimulate locomotor activity after Injection Into the substantia Innominata / lateral preoptic area. Pharmacol., Blochem., & Behav. (In press). ABSTRACTS Grund, V.R., E.C. Hyde, and P.E. Shreve (1981) Stimulation of Insulin secretion 1n dogs with the H2-histamine receptor agonist 1mprom1dine. Diabetes 30:122A. Grund, V.R., E.C. Hyde, and P.E. Shreve (1981) H2-h1stamine receptors and Insulin secretion. The Pharmacologist 23:161. Hyde, E.C., P.E. Shreve, and V.R. Grund (1982) Role of free fatty acids 1n histamine-induced insulin secretion in dogs. The Pharmacologist 24:215. Kolta, M.G., P. Shreve, V. De Souza, and N.J. Uretsky (1984) Time course of development of the enhanced behavioral and bio­ chemical response to amphetamine after amphetamine pretreatment. The Pharmacologist 26:218. Kolta, M., P. Shreve, and N.J. Uretsky (1985) Site of action of amphetamine (A) in enhancing locomotor activity (LMA) and stereotyped behavior (STB) in A-pretreated rats. The Pharmacologist 27:124. Shreve, P.E. and N.J. Uretsky (1987) a-Amino-3-hydroxy-5- methylisoxazole-4-propionate (AMPA)-induced hypermotility after Intraaccumbens injection is antagonized by y-glutamyl- amlnomethlylsulfonate(GAMS). Fed. Proc. 46:710. Shreve, P.E. and N.J. Uretsky (1988) Kainic acid (KA), a-amino- 3-hydroxy-5-methyl1soxazole-4-prop1onate (AMPA), and N-methyl-D- aspartlc add (NMDA) stimulate locomotor activity (LMA) after injection into the substantia innominata / lateral preoptic area (SI/LPO). Society for Neuroscience Abstracts 14:940. v Boldry, R.C., P.E. Shreve, and N.J. Uretsky(1988) 6,7-Dinitro- quinoxaline-2,3-dione (DNQX) and y-glutamylaminomethylsulfo­ nate (GAMS) selectively inhibit the hypermotHity response produced by activation of qulsqualic acid (QA) receptors in the nucleus accumbens (NA). Society for Neuroscience Abstracts 14:940. Shreve, P.E. and N.J. Uretsky (1988) Role of GABAerglc neurotrans­ mission in the substantia innominata / lateral preoptic area (SI/ LPO) in the hypermotility responses produced by excitatory amino acids (EAA) Injected into the nucleus accumbens (NA). The Pharmacologist 30:A25. Field of Study: Pharmacology vi TABLE OF CONTENTS PAGE DEDICATION................................................................................................................... 11 ACKNOWLEDGEMENTS..................................................................................................... 111 VITA................................................................................................................................. iv LIST OF TABLES.......................................................................................................... xii LIST OF FIGURES........................................................................................................ xiii CHAPTER I. INTRODUCTION........................................................................................................ 1 Excitatory Amino Acid Pharmacology.............................................. 1 Endogenous Excitatory amino acids........................................ 1 Excitatory Amino Acid Receptor Classification............. 2 Effects of Excitatory Amino Acids on Neurons............... 6 Excitatory Amino Acids and Long Term Potentiation... 8 Excitatory Amino Acids and Neurotoxicity........................ 9 Function and Anatomy of The Nucleus Accumbens....................... 11 Function of the Nucleus Accumbens......................................... 11 Pharmacology of Excitatory Amino Acids in the Nucleus Accumbens .............................................................................. 13 Function of the Substantia Innominata / Lateral Preoptic area....................................................................................... 15 Statement of the Problem..................................................................... 18 v i 1 CHAPTER PAGE II. Role of Quisqualic Acid Receptors in the Hypermotility Response Produced by the Injection of AMPA into the Nucleus Accumbens ...........................................................................................
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