Endocannabinoids underlie reconsolidation of hedonic memories in Wistar rats.

Rationale: Drug 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.

Objectives: The 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.

Methods: Male 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.

Results: Blockade 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.