Influence of calcium channel antagonists on nonsomatic signs of nicotine and D-amphetamine withdrawal in mice

Background: Nonsomatic signs of psychostimulant withdrawal, difficult to demonstrate in animal paradigms, may appear to promote drug seeking and drug relapse in humans; thus, it is important to understand the mechanisms that mediate this kind of behaviors. The present study was undertaken to examine the calcium-dependent mechanism of negative nonsomatic and anhedonia-related symptoms of acute and protracted withdrawal of nicotine and D-amphetamine. Methods: Mice were chronically treated with nicotine (seven days, three times daily, 3.35 mg/kg, sc) or D-amphetamine (14 days, once daily, 2.5 mg/kg, ip). Then, at the first, seventh or 14th day of withdrawal, anxiety- or depression-related effects, as well as cognition or nociception were studied. Results: Our results demonstrated that, at the seventh or 14th day of D-amphetamine or nicotine withdrawal, respectively, mice exhibited increased anxiety and depression-like effects, memory impairment and hyperalgesia. Further, major findings showed that calcium channel antagonists, i.e., nimodipine, verapamil and flunarizine (10 and 20 mg/kg, ip), injected before the test, attenuated above-mentioned signs of drug withdrawal. Conclusions: As an outcome, these findings support the hypothesis that similar calcium-dependent mechanisms are involved in an aversive nonsomatic component, associated with nicotine or D-amphetamine withdrawal. We can suggest that calcium channel blockers have potential to alleviate drug withdrawal and may thus be beneficial as pharmacotherapy of drug cessation and relapse. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.