Chronic stimulation of the tone of endogenous anandamide reduces cue-and stress-induced relapse in rats

Abstract

Background: The endogenous cannabinoid system plays an important role in motivation, stress, and drug abuse. Pharmacologically, the endocannabinoid system can be stimulated by either agonists of CB1 receptors or inhibition of metabolic degradation of endogenous cannabinoids and consequent increases in their brain levels. Methods: Here, we investigated whether chronic administration during a period of withdrawal of the fatty acid amide hydrolase inhibitor URB597, which increases anandamide levels, would decrease the risks of relapse to cocaine seeking. Rats were allowed to self-administer cocaine and then they underwent forced withdrawal for 28 days, during which they were treated with URB597 or vehicle. One day after the last injection, we investigated cocaine seeking in one 6 h extinction session and relapse triggered by re-exposure to drug-associated cues or a pharmacological stressor. Results: We found that administration of URB597 significantly decreases cocaine-seeking behavior and cue- and stressinduced relapse. Conclusion: These results suggest that stimulation of the endocannabinoid system could be helpful to prevent relapse to cocaine addiction.