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

Cannabinoid CB(1) receptor antagonists can decrease methamphetamine self-administration. This study examined whether the CB(1) 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 Delta(9)-tetrahydrocannabinol (2.0 mg/kg, i.p.)-induced hypothermia. These data fail to support a role for endogenous cannabinoids or cannabinoid CB(1) receptors in reinstatement and, therefore, relapse to stimulant abuse.