Calcium channel antagonists attenuate cross-sensitization to the rewarding and/or locomotor effects of nicotine, morphine and MK-801

Abstract

Abstract The present study focused on the evaluation of behavioural cross-sensitization, particularly in locomotor activities and conditioned rewarding effects, between nicotine and morphine, cocaine, amphetamine or MK-801. Nicotine (0.5 mg kg−1)-experienced mice manifested an enhanced locomotor response to morphine (5 mg kg−1) or MK-801 (0.3 mg kg−1). No cross-sensitization was observed between nicotine and amphetamine (2 mg kg−1) or cocaine (15 mg kg−1). Additionally, the L-type voltage-dependent calcium-channel antagonists, nimodipine and verapamil, but not diltiazem, at a dose of 20 mg kg−1 injected before morphine or MK-801 challenge, blocked the expression of this cross-sensitization. In the second test, an enhancement of morphine place conditioning in rats pre-exposed to nicotine (0.5 mg kg−1, injected daily for 5 days) was demonstrated. After two conditioning sessions, morphine (5 mg kg−1) induced a clear place preference only in animals that had previously received nicotine injections. The administration of nimodipine (10 and 20 mg kg−1), verapamil (10 and 20 mg kg−1) and diltiazem (10 and 20 mg kg−1) prior to nicotine dose-dependently prevented this sensitization to the rewarding effect of morphine produced by prior injections of nicotine. These findings support the hypothesis that similar neural calcium-dependent mechanisms are involved in the appetitive effects of nicotine and morphine and in the sensitized locomotor stimulant effects of nicotine and morphine or MK-801.