Mu. Kappa and sigma opioid agonists have been shown to exert differential effects on complex behavioral processes. The present proposal is directed towards a continuation of research in the form of support for studies designed to characterize the effects of various opioids, both alone and in combination with other drugs of abuse, on the acquisition, retention and performance of complex discriminations. The first series of proposed studies involves a continuing characterization of the effects of various opioid agonists and antagonists on the acquisition and performance of discriminations in monkeys and rats. Such data may have significant implications concerning differences in the neuronal events mediating the various behavioral actions of opioids both within and across species. While endogenous opioids are thought to modulate memory, little is known concerning the effects of opioid on memory in primates. The second series of proposed studies is designed to provide a significant amount of new information concerning the effects of various opioid agonists and antagonists on memory in monkeys. It is well-documented that other drugs of abuse (e.g., cocaine) are frequently used in combination with the opioids. In light of these data the third series of proposed studies is designed to continue our characterization of the acute effects of opioids in terms of their interactions with various drugs of abuse. The fourth series of studies will characterize the combined effects of these same drugs when the opioid is administered on a chronic basis. Such studies may have dramatic and significant implications concerning not only the behavioral consequences of polydrug abuse, but also the clinical use of some of these drugs. For example, the development of new medications to treat drug abuse and their potential use in reducing several risk factors associated with AIDS infection in intravenous drug users are clinical areas which may be affected by such drug-interaction studies. The fifth series of studies will characterize the effects of various NMDA agonists and antagonists on the acquisition, retention and performance of discriminations in monkeys. These studies are significant in that they may elucidate specific mechanisms through which certain drugs of abuse alter learning and memory. Furthermore, investigations of the behavioral properties of various drugs affecting NMDA neurotransmission will provide new information which may be of potential value in the treatment of both phencyclidine-like drug dependence and overdose.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003573-10
Application #
3208047
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1983-08-01
Project End
1995-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
10
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Type
Schools of Dentistry
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Nakamura-Palacios, E M; Winsauer, P J; Moerschbaecher, J M (2000) Effects of the cannabinoid ligand SR 141716A alone or in combination with delta9-tetrahydrocannabinol or scopolamine on learning in squirrel monkeys. Behav Pharmacol 11:377-86
Gerak, L R; Moerschbaecher, J M; Bagley, J R et al. (1999) Effects of a novel fentanyl derivative on drug discrimination and learning in rhesus monkeys. Pharmacol Biochem Behav 64:367-71
Krowicki, Z K; Moerschbaecher, J M; Winsauer, P J et al. (1999) Delta9-tetrahydrocannabinol inhibits gastric motility in the rat through cannabinoid CB1 receptors. Eur J Pharmacol 371:187-96
France, C P; Ahn, S C; Brockunier, L L et al. (1998) Behavioral effects and binding affinities of the fentanyl derivative OHM3507. Pharmacol Biochem Behav 59:295-303
Auta, J; Winsauer, P J; Faust, W B et al. (1997) Effects of negative allosteric modulators of gamma-aminobutyric acidA receptors on complex behavioral processes in monkeys. J Pharmacol Exp Ther 280:316-25
Brodkin, J; Moerschbaecher, J M (1997) SR141716A antagonizes the disruptive effects of cannabinoid ligands on learning in rats. J Pharmacol Exp Ther 282:1526-32
Pakarinen, E D; Faust, W B; Moerschbaecher, J M (1996) Effects of convulsant and anticonvulsant agents on memory in squirrel monkeys. Prog Neuropsychopharmacol Biol Psychiatry 20:883-98
Mosaddeghi, M; Kapusta, D R; Minor, L D et al. (1995) Effects of kappa-opioid receptor agonists on stimulated phosphoinositide hydrolysis in rat kidney. Eur J Pharmacol 289:411-7
Pakarinen, E D; Woods, J H; Moerschbaecher, J M (1995) Repeated acquisition of behavioral chains in squirrel monkeys: comparisons of a mu, kappa and delta opioid agonist. J Pharmacol Exp Ther 272:552-9
Burke, T F; Miller, L G; Moerschbaecher, J M (1994) Acute effects of benzodiazepines on operant behavior and in vivo receptor binding in mice. Pharmacol Biochem Behav 48:69-76

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