Endocannabinoids underlie reconsolidation of hedonic memories in Wistar rats.

rationaleDrug addicts constantly relapse to drug seeking after recall of memories linked to the drug experience. It is believed that a successful application of therapies that block memory reconsolidation may end the continuous cycle of drug relapse.

objectivesThe purpose of this study is to investigate whether modulation of the endocannabinoid system would impact the reconsolidation of opioid-related hedonic memories in rats previously paired to morphine context.

methodsMale Wistar rats were trained to acquire a morphine-conditioned place preference (CPP). One week later, morphine-CPP memory was reactivated by a brief exposure to a drug-paired context. Immediately after the memory reactivation session, independent groups of morphine-trained rats received a single subcutaneous injection of different doses of cannabinoid CB1 receptor antagonist rimonabant, CB2-selective antagonist AM630, potent CB1/CB2 agonist WIN 55,212-2, inhibitor of enzyme fatty acid amide hydrolase URB597, or vehicle. Morphine-CPP was retested 1 and 2 weeks after reactivation.

resultsBlockade of CB1 (but not CB2) cannabinoid receptors impaired CPP reconsolidation of morphine-CPP at both tests 1 and 2 weeks post-reactivation, whereas direct activation of cannabinoid receptors did not produce significant effects on morphine-induced CPP. However, boosting endocannabinoid signaling by inhibition of anandamide metabolism promoted a transient CB1-dependent enhancement of the CPP.