The motivational component of
drug withdrawal may contribute to
drug seeking and relapse through the negative reinforcement-related process; thus, it is important to understand the mechanisms that mediate affective withdrawal behaviors. The present study was undertaken to examine the
calcium-dependent mechanism of negative motivational symptoms of
nicotine and
morphine withdrawal using the conditioned place aversion (CPA) paradigm. Rats were chronically treated with
nicotine (1.168 mg/kg, free base, s.c., 11 days, three times daily) or
morphine (10 mg/kg,s.c., 11 days, twice daily). Then, during conditioning, rats pre-treated with
nicotine or
morphine received a
nicotinic receptor antagonist
mecamylamine (3.5 mg/kg) or an
opioid receptor antagonist naloxone (1 mg/kg) to precipitate withdrawal in their initially preferred compartment, or saline in their non-preferred compartment. Our results demonstrated that after three conditioning sessions,
mecamylamine induced a clear place aversion in rats that had previously received
nicotine injections, and
naloxone induced a significant place aversion in rats that had previously received
morphine injections. Further, the major findings showed that
calcium channel antagonists, i.e.,
nimodipine,
verapamil and
flunarizine (5 and 10 mg/kg, i.p.), injected before the administration of
mecamylamine or
naloxone, attenuated
nicotine or
morphine place aversion. As an outcome, these findings support the hypothesis that similar
calcium-dependent mechanisms are involved in aversive motivational component associated with
nicotine a
morphine withdrawal. We can suggest that
calcium channel blockers have potential for alleviating
nicotine and
morphine addiction by selectively decreasing the incentive motivational properties of both drugs, and may be beneficial as smoking cessation or
opioid dependence pharmacotherapies.