Rimonabant blocks the expression but not the development of locomotor sensitization to nicotine in rats

Rationale Cannabinoid, especially CB(1,) receptors have been implicated in the development and expression of a variety of behaviors produced by addictive drugs. Objectives The intent was to determine if coadministration of the selective CB(1) receptor antagonist, rimonabant (SR141716A), would block the development or expression of locomotor sensitization to repeated injections of nicotine. Materials and methods Male Long-Evans rats were injected with either 2 mg/kg rimonabant or its vehicle 30 min before an injection of 0.4 mg/kg nicotine or saline and immediately placed in activity chambers for 1 h on each of six sessions on alternating days. Before the two subsequent challenge sessions, all rats were injected with the vehicle and 0.4 mg/kg nicotine combination and then with the 2 mg/kg rimonabant and 0.4 mg/kg nicotine combination, respectively. Results Repeated injections of nicotine produced a progressive increase in locomotion that was blocked by coadministration of rimonabant. However, the subsequent nicotine challenge increased locomotion in both nicotine-pretreated groups equally more than in the saline-pretreated groups. Coadministration of rimonabant along with nicotine on the second challenge decreased the locomotion of the nicotine-pretreated rats to equal that of the saline-pretreated rats. Rimonabant had no effect on the saline-pretreated rats. Conclusion These data suggest that rimonabant blocks the expression but not the development of locomotor sensitization to nicotine.