Involvement of the endocannabinoid system in the mechanism of relapse to drug craving

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[METHAMPHETAMINE (MAP)]1)MAP-seeking_behavior:Priming injection of MAP as well as re-exposure to light and tone previously paired with MAP-taking (MAP associated-cues) reinstated MAP-seeking behavior. The reinstatement induced by MAP-priming injection was potentiated by cannabinoid (CB) receptor agonist THC and antagonized by CB1 receptor antagonist SR141716A. Furthermore, COX inhibitor diclofenac attenuated both MAP-priming-and cue-induced reinstatement. In addition, MAP-priming-injection as well as MAP associated-cues induced reinstatement were attenuated by repeated THC-injection during MAP withdrawal. Not only MAP-priming-but also cue-induced reinstatement were attenuated by microinjection of local anesthetic lidocaine or SR141716A into basolateral amygdala (BLA).2)Change in the levels og the endogenous CB receptor ligand 2-AG:The contents of 2-AG in the rat whole brain following self-administration of MAP for 10 days were increased compared with non-treated group. However, on day … More 5 of MAP withdrawal, during which only saline was available, the contents of 2-AG tended to decrease.[cocaine]Re-exposure to cocaine-associated cues reinstated cocaine-seeking behavior, and SR141716A as well as diclofenac attenuated the reinstatement. CB1 receptor agonist HU210 also reinstated cocaine-seeking behavior, and this reinstatement was attenuated by diclofenac. Furthermore, during the expression of cue-induced cocaine-seeking behavior, the contents of prostaglandin E_2 (PGE_2), an end product of the arachidonic acid cascade (AAC), in the nucleus accumbens of the cocaine-self-administering rats were increased.The aforementioned evidence, clarifies that 1)MAP/cocaine-seeking behavior were due to activation of AAC, mediated by brain CB1 receptor, and 2)BLA is one of the substrates responsible for the expression of MAP-seeking behavior. Furthermore, 3)these results not only unveil the mechanisms of the expression of drug dependence, but also implicate that various kinds of psychiatric disorders are, in part, due to dysfunction of the brain reward system. Less