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

Abstract

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.

Fig. 1

A: i.v. self-administration of 0.1mg/kg/infusion methamphetamine (M) and saline (S) in 10 rats responding under an fixed ratio 2 schedule (*P<0.05 versus M). B: responding for saline in sessions immediately preceded by i.v. administration of methamphetamine (*P<0.05 versus S in left panel). C: responding for saline in sessions immediately preceded by 0.1 mg/kg of methamphetamine and AM251. Ordinate: average number of infusions received for 10 rats. Abscissae: B and C, dose in mg/kg.

Fig. 2

Average body temperature (°C) for 8 rats before (0) and for 120 min after administration of 0.32 mg/kg AM251 and 2.0 mg/kg THC alone or together.