The overall objective of the proposed research is to characterize the effects of cannabinoids on complex, discrimination tasks involving learning and memory in nonhuman primates. A repeated acquisition and delayed performance procedure will be used to assess the effects of cannabinoids on memory in monkeys. These studies will enhance our understanding of how the cannabinoids affect complex behavioral processes and cognition. The first series of proposed studies are specifically aimed at continuing and extending our studies of the effects of various cannabinoid agonists and antagonists on the acquisition and performance of discriminations in monkeys. Specifically, acute dose-effect curves for the agonists 69-THC, CP55,940, cannabidiol, and R-methanandamide and the antagonist SR141716A will be determined. Each agonist will then be tested in combination with BR141716A in order to characterize the nature of the antagonism. These studies are designed to test the hypothesis that the cannabinoid receptor system plays a role in modulating cognitive processes involved in learning. The second series of studies will characterize the acute effects of these same cannabinoid agonists on memory in monkeys. Specifically, these studies will evaluate the amnestic effects of these drugs and their actions on storage and retrieval processes following both short and long delays. These studies are designed to test the hypothesis that the cannabinoid receptor system plays a role in modulating cognitive processes involved in memory. Because polydrug abuse continues to be a major health-care problem, the third series of studies involves the acute characterization of cannabinoids in combination with other prototypical drugs of abuse. Specifically, cannabinoid ligands will be investigated in combination with opioids (heroin, methadone & buprenorphine), stimulants (cocaine, amphetamine & nicotine), and sedative-hypnotics (lorazepam 8 pentobarbital). These studies are designed to test the hypothesis that the effects of the cannabinoids on learning and memory are potentiated by other drugs of abuse. Together these studies will provide new information that will be of direct relevance to the clinical management of the cannabinoid user. In addition, studies involving the actions of the cannabinoid receptor antagonist alone will provide valuable data concerning the potential use of this and related agents in the pharmacotherapy of cannabinoid abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA011417-01A1
Application #
2694509
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Schnur, Paul
Project Start
1999-07-01
Project End
2004-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Pharmacology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Quinton, M S; Gerak, L R; Moerschbaecher, J M et al. (2006) Effects of pregnanolone in rats discriminating cocaine. Pharmacol Biochem Behav 85:385-92
Quinton, M S; Gerak, L R; Moerschbaecher, J M et al. (2005) Interaction of cocaine with positive GABAA modulators on the repeated acquisition and performance of response sequences in rats. Psychopharmacology (Berl) 181:217-26
Winsauer, P J; Quinton, M S; Porter, J R et al. (2004) Effects of MDMA administration on scopolamine-induced disruptions of learning and performance in rats. Pharmacol Biochem Behav 79:459-72
Winsauer, P J; Moerschbaecher, J M; Molina, P E et al. (2003) Contingent and noncontingent cocaine administration in rhesus monkeys: a comparison of the effects on the acquisition and performance of response sequences. Behav Pharmacol 14:295-306
Daniel, Jill M; Winsauer, Peter J; Moerschbaecher, Joseph M (2003) Castration in rats impairs performance during acquisition of a working memory task and exacerbates deficits in working memory produced by scopolamine and mecamylamine. Psychopharmacology (Berl) 170:294-300
Daniel, Jill M; Winsauer, Peter J; Brauner, Ian N et al. (2002) Estrogen improves response accuracy and attenuates the disruptive effects of delta9-THC in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance. Behav Neurosci 116:989-98
Winsauer, Peter J; Delatte, Marcus S; Stevenson, Michael W et al. (2002) Effects of triazolam, 8-OH-DPAT, and buspirone on repeated acquisition in squirrel monkeys. Exp Clin Psychopharmacol 10:392-9
Delatte, M S; Winsauer, P J; Moerschbaecher, J M (2002) Tolerance to the disruptive effects of Delta(9)-THC on learning in rats. Pharmacol Biochem Behav 74:129-40
Winsauer, Peter J; McCann, Una D; Yuan, J et al. (2002) Effects of fenfluramine, m-CPP and triazolam on repeated-acquisition in squirrel monkeys before and after neurotoxic MDMA administration. Psychopharmacology (Berl) 159:388-96