Δ9-Tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats

On the basis of contradictory findings on the rewarding effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in laboratory animals, the effect of the compound on conditioned place preference and intracerebroventricular (i.c.v.) self-administration in a free-choice procedure, using a wide range of doses (0.015-6 mg/kg for conditioned place preference test and 0.01-1 mug/2 mul/infusion for i.c.v. self-administration), was studied in Wistar rats. The present results showed that Delta(9)-THC induced reward in both tests, but only at the lowest tested doses (0.075-0.75 mg/kg i.p. for conditioned place preference test and 0.01-0.02 mug/infusion for i.c.v. self-administration). This effect was fully antagonised by i.p. pretreatment with the cannabinoid CB1 receptor antagonist, SR 141716A [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichlorophenyl)-4 methyl pyrazole 3-carboxamide] (0.25-1 mg/kg), and the opiate receptor antagonist, naloxone (0.5-2 mg/kg), suggesting the involvement of both endocannabinoid and opioid systems. In conclusion, these findings demonstrate, for the first time, that low doses of Delta(9)-THC can act as an effective reinforcer in Wistar rats providing a reliable animal model of human marijuana abuse. (C) 2004 Elsevier B.V. All rights reserved.