Calcium-dependent mechanisms of the reinstatement of nicotine-conditioned place preference by drug priming in rats

Reinstatement of drug-seeking behaviour in animals is relevant to relapse to drug taking in humans. We used the conditioned place preference version of the reinstatement model to investigate the establishment, extinction, reinstatement and cross-reinstatement of nicotine-induced place conditioning in rats. Nicotine produced a place preference to the 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, nicotine-experienced rats were challenged with nicotine (0.5 mg/kg, i.p.), a cannabinoid receptor agonist WIN55,212-2 (0.5 mg/kg, i.p.), ethanol (0.5 g/kg, i.p.) or d-amphetamine (2 mg/kg, i.p.). The priming injections of nicotine, WIN55,212-2 and ethanol, but not of d-amphetamine renewed a preference for the compartment previously paired with nicotine. Finally, we examined the influence of the calcium channel antagonists, nimodipine (5 and 10 mg/kg, i.p.) and flunarizine (5 and 10 mg/kg, i.p.), on the reinstatement of nicotine place conditioning induced by WIN55,212-2 and ethanol. It was shown that the calcium channel blockers attenuated the reinstatement of nicotine-conditioned response induced by both drugs. As reinstatement of drug-seeking is a factor for the development of dependence, the L-type calcium channel antagonists may be useful in the relapse-prevention phase of addiction treatment, including cannabinoid, ethanol, and/or nicotine dependence.