Reinstatement of nicotine-conditioned place preference by drug priming: effects of calcium channel antagonists

Abstract

Reinstatement of drug-seeking behaviour in animals is relevant to drug relapse in humans. In the present study, we used the conditioned place preference paradigm to investigate the establishment, extinction, reinstatement and cross-reinstatement of nicotine-induced place conditioning in rats. Nicotine produced a place preference to the initially less-preferred compartment paired with its injections during conditioning (0.5 mg/kg, i.p., three drug sessions). Once established, nicotine place preference was extinguished by repeated training. Following this extinction phase, the reinstatement of place conditioning was investigated. For this purpose, nicotine-experienced rats were challenged with nicotine (0.5 mg/kg, i.p.) or morphine (10 mg/kg, i.p.). These priming injections of both drugs renewed a marked preference for the compartment previously paired with nicotine. In the second step, we examined the influence of the calcium channel antagonists, nimodipine (10 and 20 mg/kg, i.p.) and flunarizine (5 and 10 mg/kg, i.p.), on the reinstatement of nicotine-conditioned place preference induced by priming doses of nicotine and morphine. It was shown that the calcium channel blockers dose dependently attenuated the reinstatement of nicotine place preference induced by both drugs. These findings support the hypothesis that similar neural calcium-dependent mechanisms are involved in nicotine- and morphine-induced reinstatement. Finally, the conditioned place preference paradigm appears to be a useful tool for studies of the relapse of drug-seeking behaviour in laboratory animals.