The ability of drugs of abuse to affect cognitive processes in both laboratory animals and humans is now well documented, Yet, the mechanism for this effect is not understood. This project will focus on the effects of three drugs of abuse (diazepam, pentobarbital and phencyclidine) on memory function as determined by two operant schedules of reinforcement: a delayed alternation schedule and a delayed matching- to-sample schedule. These drugs have been shown to bind to specific sites in the brain: diazepam has been shown to bind to the GABA chloride channel complex, pentobarbital has been shown to bind at the GABA channel complex, as well as the AMPA activated channel and to the sigma binding site. However, there is little information available about the relative role of each of these sites in the modulation of memory function by these drugs. Thus, the overall goal of this project is to determine the role of these binding sites in the effect of the drugs on memory function. The behavior of rats, pigeons and squirrel monkeys will be maintained under a delayed alternation schedule and a delayed matching-to-sample schedule. Once responding has stabilized and dose-response curves have been etermined for diazepam, pentobarbital and phencyclidine, the role of the GABA receptor complex in mediating the effects of the three drugs on memory will be explored by using selected doses of RO 15-4513, and picrotoxin. The role of the NMDA activated channel and the PCP receptor will be examined by using selected doses of NMDA and CGS 19755. The role of the AMPA activated channel will be determined by using selected doses of NBQX, and the role of the sigma binding site will be studied by using selected doses of DTG, haloperidol and BMY 14802. These experiments will provide data relevant to determining the locus of action of three drugs of abuse and what if any commonalities exist between them. Understanding the locus/mechanism of action of these drugs of abuse on memory function will provide a more complete picture of the pharmacology of human drug abuse.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
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University of Arkansas for Medical Sciences
Schools of Medicine
Little Rock
United States
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Nordholm, A F; Moore, E; Wenger, G R (1995) Linopirdine does not improve matching performance in the titrating matching-to-sample paradigm. Pharmacol Biochem Behav 52:205-10