A cannabinoid mechanism in relapse to cocaine seeking

Treatment of cocaine addiction is hampered by high rates of relapse even af ter prolonged drug abstinence. This relapse to compulsive cocaine use can b e triggered by re-exposure to cocaine(1), by re-exposure to stimuli previou sly associated with cocaine(2) or by exposure to stress(3). In laboratory r ats, similar events reinstate cocaine seeking after prolonged withdrawal pe riods', thus providing a model to study neuronal mechanisms underlying the relapse to cocaine. The endocannabinoid system has been implicated in a num ber of neuropsychiatric conditions, including drug addiction(7,8). The acti ve ingredient of marijuana, Delta9-tetrahydrocannabinol, activates the meso limbic dopamine (DA) reward system(9,10) and has rewarding effects in precl inical models of drug abuse(8,11,12). We report here that the synthetic can nabinoid agonist, HU210 (ref. 13), provokes relapse to cocaine seeking afte r prolonged withdrawal periods. Furthermore, the selective CB1 receptor ant agonist, SR141716A (ref. 14), attenuates relapse induced by re-exposure to cocaine-associated cues or cocaine itself, but not relapse induced by expos ure to stress. These data reveal an important role of the cannabinoid syste m in the neuronal processes underlying relapse to cocaine seeking, and prov ide a rationale for the use of cannabinoid receptor antagonists for the pre vention of relapse to cocaine use.