Sub-chronic administration of AM251, CB1 receptor antagonist, within the nucleus accumbens induced sensitization to morphine in the rat

It seems that there is a cross-talk between the cannabinoid CB1 and opioid receptors in the process of sensitization to opiates. In present study, we tried to examine the effect of solely administration of AM251, a CB1 receptor antagonist, on conditioned place preference (CPP) by ineffective dose of morphine in the rat. 102 adult male albino Wistar rats were used in these experiments. Subcutaneous administration of morphine (0.5, 1, 2.5, 5, 7.5 and 10 mg/kg) induced CPP only at the doses of ≥5 mg/kg. The dose of 0.5 mg/kg of morphine was selected as the appropriate (ineffective) dose for induction of CPP in animals which were previously received AM251 (5, 25 and 125 ng/0.5 μl per side) once daily for three days as a sub-chronic administration or those that received a single dose on the test day. Bilateral intra-accumbal sub-chronic but not single administration of AM251 dose-dependently produced sensitization to morphine and induced CPP by ineffective dose of morphine (0.5 mg/kg) in the rat. Bilateral intra-accumbal administration of neither saline nor DMSO (0.5 μl/side) had effects on sensitization to morphine. Our findings indicated that CB1 receptors within the nucleus accumbens are involved in the sensitization to morphine in rats.