title: Influence of calcium channel antagonists on nonsomatic signs of nicotine and D-amphetamine withdrawal in mice.
abstract: 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, 2.5mg/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.
  
  
  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 20mg/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.
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland. Electronic address: grazyna.biala@umlub.pl.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Biała
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Polak
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Michalak
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kruk-Słomka
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Budzyńska
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D015220:Calcium Channels / Q000502:physiology; D003863:Depression / Q000209:etiology / Q000517:prevention & control; D003913:Dextroamphetamine / Q000009:adverse effects*; D008568:Memory / Q000187:drug effects; D051379:Mice; D009538:Nicotine / Q000009:adverse effects*; D059225:Nociception; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009538:Nicotine; D002118:Calcium; D003913:Dextroamphetamine
keywords: Calcium channel antagonists; Mice; Nicotine; Withdrawal; d-Amphetamine