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

Grażyna Biała, Piotr Polak, Agnieszka Michalak, Marta Kruk-Słomka, Barbara Budzyńska

Index: Pharmacol. Rep. 66(2) , 212-22, (2014)

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Abstract

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.Mice were chronically treated with nicotine (seven days, three times daily, 3.35 mg/kg, sc) or D-amphetamine (14 days, once daily, 2.5mg/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.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 20mg/kg, ip), injected before the test, attenuated above-mentioned signs of drug withdrawal.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.Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.