INFORMATION TO USERS This manuscript has been reproduced 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 bleed through, 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. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. A Bell & Howell information Company 300 Norm Z eeb Road. Ann Arbor. Ml 48106-1346 USA 313/761-4700 800/521-0600 Modulation of cortical ACh release by GABAA-dopamine receptor interactions in the basal forebrain DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the Graduate School of The Ohio State University by Holly Moore, B.S. The Ohio State University 1995 Dissertation Committee: Approved by John P. Bruno, Ph.D. Martin Sarter, Ph.D. Lane Wallace, Ph.D. Bennett Givens, Ph.D. / Advisor ( Neuroscience Program Department of Psychology UMI Number: 9544646 OMI Microform 9544646 Copyright 1995, by UMI Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. UMI 300 North Zeeb Road Ann Arbor, Ml 48103 ACKNOWLEDGEMENTS I sincerely thank my mentors, Dr. John P. Bruno and Dr. Martin Sarter for their guidance. Being a part of their scientifric collaboration has been an honor an enriching experience. Thanks to Dr. James King and to members of the Neuroscience Graduate Studies Committee for their creative energies and perserverance in continually increasing the quality of the Neuroscience Graduate Program. I also thank my dissertation committee for their interest in this project and their important suggestions. Special acknowledgements are made to Lee Ann Holley Miner for her constant generous offering of computer equipment, transportation, moral support and academic enlightenment, to Kathlene R. Merendo for her insight and resourcefulness, and to Scott Stuckman for his efforts on this project. Finally, I offer unending gratitude to my family for their patience and support. ii To Leslie, Marcia, Hope, Virginia and Grace, my constant sources of inspiration. iii VITA December 14, 1962 Born, Urbana, Ohio 1990 B.S. Wright State University; dual degree in Psychology and Chemistry 1990-present The Ohio State University Graduate School Neuroscience Ph.D. Program RESEARCH PUBLICATIONS Bruno, J.P., Moore, H., Dudchenko, P., & Sarter, M. (1992). Modulation of frontal cortical acetylcholine release by benzodiazepine receptor ligands: Age-dependent effects and behavioral correlates. In E.M. Meyer, F.T. Crews, & J.W. Simpkins (Eds.), The treatment of dementias: A new generation of progress. NY: Plenum Press, pp. 277- 298. Moore, H., Dudchenko, P., Bruno, J.P., & Sarter, M. (1992). Towards modelling age-related changes of attentional abilities in rats: simple and choice reaction time tasks and vigilance. Neurohiol Aging. 12., 759-772. Moore, H., Dudchenko, P., Comer, K.S., Bruno, J.P., & Sarter, M. (1992). Central versus peripheral effects of muscarinic antagonists: the limitations of quaternary ammonium derivatives. Psvchopharmacolog v. 108. 241-243. Moore, H., Sarter, M., & Bruno, J.P. (1992). Age-dependent modulation of in vivo cortical acetylcholine release by benzodiazepine receptor ligands. Brain Research. 596. 17-29. iv Tamborski, A., Moore, H., Lucot, J.B., Hennessy, M. (1993). Monoamine activity in anterior hypothalamus of guinea pig pups separated from their mothers. Behavioral Neuroscience. 108, 171-176. Bruno, J.P., Moore, H., Stuckman, S., Johnson, B. & Sarter, M. (1994). Repeated microdialysis sampling as a valid technique to study cortical and striatal acetylcholine efflux. Current Separations. 15, 1-3. Moore, H., Sarter, S. & Bruno, J.P. Bidirectional modulation of cortical acetylcholine release by infusion of benzodiazepine receptor ligands into the basal forebrain. Neuroscience Letters. 189. 31-34 Moore, H., Stuckman, S., Sarter, M., & Bruno, J.P. (1995). Stimulation of cortical acetylcholine efflux by FG 7142 measured with repeated microdialysis. Synapse. 21, 71-76. PUBLISHED ABSTRACTS Moore, H., Sarter, M., and Bruno, J.P. (1990). GABAergic mediation of frontal cortical acetylcholine release in awake rats. Current Separations. 10. Abstract #19. Moore, H., Berntson, G., Sarter, M. & Bruno, J.P. (1991). Age dependent modulation of cortical acetylcholine release by benzodiazepine ligands. Presented at the Society for Neuroscience 21st Annual Meeting. Abstract 632.8. Quigley, K., Moore, H., Dudchenko, P., Bruno, J.P., & Sarter, M. (1991). Age-related changes in attentional abilities in Fischer-344 rats: Effects of benzodiazepine receptor ligands and amphetamine. Society for Neuroscience 21st Annual Mtg.. Abtract 116.15. Sarter, M., Dudchenko, P., Moore, H., & Bruno, J.P. (1991). Cognition enhancement based on GABA-cholinergic interactions. Satellite Symposium: Neurotransmitter Interactions and Cognitive Function. Society for Neuroscience 21st Annual Meeting. New Orleans, LA. Sarter, M., Moore, H., Dudchenko, P., & Bruno. J.P. (1991). Disinhibition of cortical cholinergic activity and attenuation of age-related attentional impairments. American Federation for Aging Research Grantee Conference. NY, NY. v Moore, H., Berntson, G., Sarter, M. & Bruno, J.P. (1991). Age dependent modulation of cortical acetylcholine release by benzodiazepine ligands. Presented at the Society for Neuroscience 21st Annual Meeting. Abstract 632.8. Quigley, K., Moore, H., Dudchenko, P., Bruno, J.P., & Sarter, M. (1991). Age-related changes in attentional abilities in Fischer-344 rats: Effects of benzodiazepine receptor ligands and amphetamine. Society for Neuroscience 21st Annual Mtg.. Abtract 116.15. Sarter, M., Dudchenko, P., Moore, H., & Bruno, J.P. (1991). Cognition enhancement based on GABA-cholinergic interactions. Satellite Symposium: Neurotransmitter Interactions and Cognitive Function. Society for Neuroscience 21st Annual Meeting. New Orleans, LA. Sarter, M., Moore, H., Dudchenko, P., & Bruno. J.P. (1991). Disinhibition of cortical cholinergic activity and attenuation of age-related attentional impairments. American Federation for Aging Research Grantee Conference. NY, NY. Tamborski, A., Lucot, J.B., Moore, H., & Hennessy, M.B. (1991). Catecholamine turnover in anterior hypothalamus of guinea pig pups separated from their mothers in a novel environment. Presented at International Society for Developmental Psychobiology. New Orleans, LA. Moore, H., Sarter, M., & Bruno, J.P. (1992). Interactions between environmental manipulations and benzodiazepine receptor ligands on cortical acetylcholine release. Society for Neuroscience 22nd Annual Meeting. Abstract 47.2. Bruno, J.P., Moore, H., and Sarter, M. (1993). FG 7142, a negative modulator at the GABAA/Benzodiazepine receptor, increases cortical acetylcholine efflux: Interactions with dopamine receptor ligands. Society for Neuroscience 23nd Annual Meeting. Abstract 128.11. Moore, H., Sarter, M., and Bruno, J.P. (1993). Benzodiazepine receptor mediation of cortical acetylcholine efflux: The determining roles of vi environmental/behavioral manipulations. Curr Separations. 12, Abstract # 47. Moore, H., Sarter, M. & Bruno, J.P. (1993). Modulation of stimulated cortical acetylcholine efflux by benzodiazepine receptor ligands is mediated in the basal forebrain. Society for Neuroscience 23nd Annual Meeting. Abstract 128.12. Moore, H., Stuckman, S., Sarter, M. and Bruno, J.P. (1993). Modulation of cortical ACh efflux by GABA/benzodiazepine receptor ligands: Effects of repeated testing and interactions with dopamine receptors. Current Separations. 12, Abstract ft 8. Sarter, M., Bruno, J.P., Moore, H., McGaughy, J., Dudchenko, P., Holley, L.A. and Turchi, J. (1993). Basal forebrain GABAergic modulation of cortical acetylcholine release and of attentional abilities. British Association for Psvchopharmacologv. Cambridge, U.K. Stuckman, S., Moore, H., Berntson, G., Sarter, M. and Bruno, J.P. (1993). Effect of repeated microdialysis testing on stimulated cortical acetylcholine efflux. Society for Neuroscience 23nd Annual Meeting. Abstract 128.13. Moore, H., Stuckman, S., Sarter, M. & Bruno, J.P. (1994). Stimulation of cortical ACh efflux by local ionic changes, but not local muscarinic blockade, is diminished in aged rats. Society for Neuroscience 24th Annual Meeting. Bruno, J.P., Sarter, M., Moore, H. & Fadel, J. (1995). Trans-synaptic modulation of cortical acetylcholine release: A new approach to restore cholinergic function. Neurodegenerative Disorders: