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Psychopharmacology

ISSN: 0033-3158 (printed version)
ISSN: 1432-2072 (electronic version)

Table of Contents 
Abstract Volume 137 Issue 2 (1998) pp 147-156

original investigation: A detailed characterization of the effects of four cannabinoid agonists on operant lever pressing

D. Carriero, J. Aberman, S. Y. Lin, A. Hill, A. Makriyannis, J. D. Salamone

Department of Psychology and School of Pharmacy, University of Connecticut, Storrs, CT 06269-1020, USA

Received: 16 May 1997 / Final version: 2 December 1997

Abstract
The present experiments were conducted to investigate the effects of four cannabimimetics on detailed temporal parameters of operant responding. In this study, the behavioral output during performance of a fixed ratio 5 schedule of reinforcement was recorded by a computer program that measured the response initiation time (IT; time interval between the offset of one lever press and the onset of the next) and the response duration (the amount of time that elapses from the onset to the offset of one lever press) of each lever press. ITs were further partitioned into fast responses (IT=0.0-1.0 s), short pauses (IT=1.0-2.5 s), and long pauses (IT>2.5 s). Four cannabimimetic agents were assessed in this study: (R)-methanandamide (AM 356), a hydrolytically stable analog of arachidonylethanolamide, an endogenous ligand for the CB1 receptor; CP-55,940, a potent non-classical synthetic ligand; (-)-<Delta>8-tetrahydrocannabinol (<Delta>8-THC), an isomer of the naturally occurring <Delta>9-THC; and WIN 55,212-2, a synthetic aminoalkylindole. All four of the cannabimimetic drugs tested significantly suppressed operant lever pressing in a dose dependent manner. The rank order of potencies observed in the present study was CP-55,940>>WIN-55,212-2><Delta>8-THC>AM 356, which is consistent with the rank order of affinities for the CB1 receptor shown by these drugs. All of the cannabimimetics substantially increased average IT, and also increased duration time. There was a substantial increase in average length of long pauses, and statistically significant but very small changes in the local rate of responding as measured by the average length of fast ITs. Cannabinoid-treated rats were largely immobile during pauses in responding, and these animals showed several signs of ataxia and catalepsy at the doses that suppressed lever pressing. Together with other data, the present results suggest that CB1 stimulation leads to motor effects that are associated with a suppression of lever pressing.

Key words Tetrahydrocannabinol · THC · Anandamide · Catalepsy · Motor · Response initiation

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Online publication: April 30, 1998
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