The cannabinoid CB1 receptor antagonist AM251 does not modify methamphetamine reinstatement of responding

摘要

Cannabinoid CB1 receptor antagonists can decrease methamphetamine self administration. This study examined whether the CB1 receptor antagonist AM251 [N-(piperidin-1-yl)-5-(4-indophonyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] modifies reinstatement in rats that previously self-administered methamphetamine. Rats (n=10) self administered methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 2 schedule. Non-contingent methamphetamine (0.01-1.78 mg/kg, i.v.) yielded responding for saline (reinstatement) that was similar to responding for self-administered methamphetamine. AM251 (0.032-0.32, i.v.) did not affect methamphetamine-induced reinstatement but significantly attenuated Δ⁹-tetrahydrocannabinol (2.0 mg/kg, i.p.)-induced hypothermia. These data fail to support a role for endogenous cannabinoids or cannabinoid CB1 receptors in reinstatement and, therefore, relapse to stimulant abuse.