The long-term objective is to characterize, on complex behavioral processes such as learning and memory, the effects of different therapeutically useful opioids which are subject to abuse. Drug effects on complex behavioral tasks in non-human primates is the major focus of investigation. A multiple schedule of repeated acquisition and performance of conditional discriminations will be used in order to make a direct comparison of drug effects on learning and performance. In addition, a fixed-ratio discrimination will be used to characterize the acute and chronic effects of these same drugs in different species. Opioids (sigma agonists) which produce psychotomimetic effects in man disrupt accuracy of responding under both of these procedures in patas and macaque monkeys. This action is not shared by other opioids (mu and kappa agonists), at doses which produce approximately equivalent rate-decreasing effects. Similar differential effects do not, however, obtain in the rat. Since species differences such as these may have important implications in terms of the mechanism(s) of action of these drugs the first series of studies will characterize the effects of various opioids (e.g., morphine, buprenorphine, cyclazocine, NANM) in squirrel monkeys responding under these same behavioral procedures. The isomers of NANM and cyclazocine will also be studied in order to determine the extent to which they may affect either accuracy or rate of responding in a steroselective manner. Relatively little is known concerning the behavioral consequences of polydrug abuse. The second series of proposed experiments will continue our studies of how the opioids in combination with other drugs of abuse effect the acquisition and performance of complex discriminations. Methadone and buprenorphine will each be studied in combination with four different drugs of abuse (cocaine, larazepam, phencyclidine, pentobarbital). Each interaction will be characterized on both an acute and chronic basis. The third series of experiments will investigate the development of tolerance to each of the isomers of cyclazocine. In addition, cross-tolerance will also be tested to other opioids and their isomers. The study of stereoselective tolerance and cross-tolerance can provide unique information concerning the mechanism(s) of action of the opioids. In addition, such studies may elucidate other behavioral determinants of the development of tolerance to abused drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003573-07
Application #
3208045
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1983-08-01
Project End
1990-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Type
School of Medicine & 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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