Disulfiram impairs the development of behavioural sensitization to the stimulant effect of ethanol

Background: Although disulfiram has been used in the treatment of alcoholism due to the unpleasant sensations its concomitant ingestion with ethanol provokes, some patients reported stimulant effects after its ingestion. This issue has not been addressed in studies with animals. in mice, the stimulant effect of ethanol has been associated with increased locomotor activity and behavioural sensitization. This study sought to analyze the influence of disulfiram on the development of behavioural sensitization to the stimulant effect of ethanol.Methods: Male Swiss mice pre-treated with vehicle or disulfiram (15 mg/kg) received saline or ethanol (2.0 g/kg) every other day, for 5 days. Forty-eight hours afterwards mice were challenged with Saline, and 48 h later they received Disulfiram, or Disulfiram + Ethanol or Ethanol.Results: the co-administration of disulfiram (15 mg/kg) blocked the development of behavioural sensitization induced by ethanol (2.0 g/kg). Although the acute administration of disulfiram did not alter the locomotor activity, its acute administration-induced higher levels of locomotor activity in mice previously sensitized to ethanol than in controls which received saline.Conclusions: Our data suggest that besides the known psychological effects (fear of aversive effects) disulfiram efficacy on alcohol dependency treatment could also be due to its pharmacological interference in the brain neurotransmission. (C) 2009 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)AFIPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilFAPESP: 04/12448-7FAPESP: 05/57295-6Web of Scienc