The overall objective of the proposed research is to characterize the effects, on complex behavioral processes, of different benzodiazepines which are used therapeutically and are subject to both acute and chronic abuse. Despite the dependence-producing potential of the benzodiazepines and the distinct behavioral effects associated with their acute and chronic use in man, there has been no systematic investigation or comparison of their effects on complex behavioral processes such as learning and memory. Complex operant tasks involving both the acqusition and performance of discriminations in nonhuman primates and rats will be the major focus of investigation. In monkeys, a multiple schedule will be used in order to make a direct comparison of the effects of various benzodiazepines on the acquisition and performance of conditional discriminations. Similarly, a multiple schedule of stimulus-duration and fixed-ratio discriminations will be used in order to directly compare the effects of these same drugs on temporal and response-based discriminations. Parallel studies will be conducted in rats. In the first series of experiments, the acute effects of """"""""long: (diazepam, flurazepam), """"""""intermediate"""""""" (lorazepam, oxazepam), and """"""""short"""""""" (midazolam, triazolam) acting benzodiazepines on learning and performance will be determined. As a comparison, the acute effects of pentabarbital and phenobarbital will also be examined. In related studies it will be determined whether the effects of the benzodiazepines on accuracy and rate of responding exhibit stereospecificity. In a second series of experiments the acute effects of various doses of diazepam, oxazepam, triazolam and pentobarbital will each be tested in combination with various doses of the specific benzodiazepine antagonist RO15-1788. The purpose of these studies is to determine the extent to which the effects of these drugs on accuracy and rate of responding are mediated by a specific mechanism of action. Finally, the chronic effects of diazepam and lorazepam will be investigated. The purpose of these studies is to characterize both the chronic (eg., behavioral tolerance) and postchronic (eg., behavioral dependence) effects of these drugs on complex behavioral processes. Together, these studies will generate a significant amount of new information concerning how both the acute and chronic administration of various benzodiazepine may affect the learning and performance of complex behavioral tasks.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA004775-01
Application #
3210475
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1987-09-01
Project End
1992-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
1
Fiscal Year
1987
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
Gerak, Lisa R; Stevenson, Michael W; Winsauer, Peter J et al. (2004) Effects of pregnanolone alone and in combination with other positive GABAA modulators on complex behavior in rats. Psychopharmacology (Berl) 173:195-202
Winsauer, P J; Moerschbaecher, J M (2000) Differential effects of 5-HT agonists and antagonists on the repeated acquisition and performance of response sequences in monkeys. Behav Pharmacol 11:535-53
Winsauer, P J; Silvester, K R; Moerschbaecher, J M et al. (2000) Cocaine self-administration in monkeys: effects on the acquisition and performance of response sequences. Drug Alcohol Depend 59:51-61
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
Winsauer, P J; Rodriguez, F H; Cha, A E et al. (1999) Full and partial 5-HT1A receptor agonists disrupt learning and performance in rats. J Pharmacol Exp Ther 288:335-47
Winsauer, P J; Lambert, P; Moerschbaecher, J M (1999) Cannabinoid ligands and their effects on learning and performance in rhesus monkeys. Behav Pharmacol 10:497-511
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
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

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