Effects of CB1 receptor antagonist within the nucleus accumbens on the acquisition and expression of morphine-induced conditioned place preference in morphine-sensitized rats

It has been shown that cannabinoids interact with the opiate system in reward-related behaviors and in animal models of addiction. In the present study, the effects of bilateral intra-accumbal administration of AM251, a CB1 receptor antagonist, on the acquisition and expression of ineffective dose of morphine-induced conditioned place preference (CPP) in morphine-sensitized rats were investigated. 158 adult male albino Wistar rats were used in these experiments. Subcutaneous (s.c.) administration of morphine (0.25, 0.5, 0.75, 1, 2.5 and 5 mg/kg) induced CPP only at the dose of 5 mg/kg. In addition, repeated administration of morphine (5 mg/kg; s.c.), once daily for 3 days followed by 5 days free of the opioid (sensitization period), increased conditioning response induced by ineffective doses of morphine (0.25, 0.5 and 0.75 mg/kg). Bilateral intra-accumbal administration of AM251 (5, 25 and 125 ng/0.5 μl per side) dose-dependently reduced the acquisition and expression of morphine-induced CPP in morphine-sensitized rats, while bilateral intra-accumbal administration of neither saline nor DMSO (0.5 μl/side) had effects on the acquisition and expression of morphine-induced CPP in sensitized rats. The results indicated that CB1 receptors within the nucleus accumbens are involved in the acquisition and expression of morphine-induced CPP in sensitized rats. Our findings also suggest the existence of cross-talk between cannabinoids and opiates on the sensitization to morphine and the implication of endocannabinoid system in the process of sensitization to opiates.