Differential involvement of the endocannabinoid system in short- and long-term expression of incentive learning supported by nicotine in rats

Rationale We previously reported that the CB1 cannabinoid receptor antagonist, rimonabant, impaired the acquisition and the short-term ( 24 h), but not long-term ( 3 weeks), expression of conditioned place preference (CPP) induced by nicotine in rats. Objective To assess the time interval of efficacy of a single pretest injection of rimonabant to abolish nicotine-CPP, and the effects of chronic CB1 receptor blockade on long-term expression of nicotine-CPP. Materials and methods Wistar rats were conditioned to nicotine (0.06 mg/kg, subcutaneous) using an unbiased one-compartment procedure. Two test sessions were conducted 24 h ( without injection) and 1, 2, or 3 weeks later. Rimonabant ( 3 mg/kg, intraperitoneal) or vehicle was administered daily between the two test sessions. In addition, the CB1-stimulated [S-35] GTP-gamma-S binding was assessed in rats from the 3-week experiment. Results The capacity of a single injection of rimonabant ( 3 mg/kg, 30 min pretest) to block the expression of nicotine-CPP disappeared within 1 week after conditioning. Daily administrations of rimonabant for 6, 13, or 20 days postacquisition did not impair nicotine-CPP but allowed an additional pretest injection of rimonabant to retain its capacity to abolish long-term expression of nicotine-CPP. The CB1 receptor-mediated G-protein signaling was not altered in various brain areas of rats given rimonabant for 3 weeks. Conclusions The endocannabinoid system is essential to the expression of nicotine-CPP during less than 1 week after conditioning but not later. However, endocannabinoid-dependent mechanisms are critically involved in the development of the neuroadaptive changes responsible for the shift from CB1-dependent to CB1-independent expression of nicotine incentive learning.