Effects of co-administration of bupropion and nicotine or D-amphetamine on the elevated plus maze test in mice

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A variety of abused drugs, including psychostimulants, can modulate the expression of anxiety. Although the effect of nicotine and D-amphetamine on anxiety-related behaviour in animal models has been investigated, the mechanisms underlying the anxiogenic or anxiolytic actions of these drugs have not been clarified. Bupropion is an antidepressant drug which may alleviate some symptoms of nicotine withdrawal, although its effects on anxiety are not clear. We have investigated the effect of nicotine and D-amphetamine on anxiety in the elevated plus maze test in mice. We examined the influence of acute administration of nicotine (0.1 mg/kg, s.c.) and D-amphetamine (2 mg/kg, i.p.) on anxiety level. We then evaluated the anxiety-related response after subchronic injection of both psychostimulants, including crossover effects. For this purpose, nicotine (0.1 mg/kg, s.c.) was administered daily for six days, and on the seventh day mice were challenged with nicotine (0.1 mg/kg, s.c.) or D-amphetamine (2 mg/kg, i.p.). A distinct group of mice was pretreated with D-amphetamine (2 mg/kg, i.p., 8 days), and subjected to D-amphetamine (2 mg/kg, i.p.) or nicotine (0.1 mg/kg, s.c.) challenge on the ninth day. Moreover, we investigated acute and subchronic effects of coadministration of bupropion (5, 10 and 20 mg/kg; i.p.) and nicotine or D-amphetamine. We observed that acute anxiogenic effects of nicotine and D-amphetamine as well as the development of tolerance and cross-tolerance to their effects were blunted by a pretreatment with a nonactive dose of bupropion (5 mg/kg, i.p.). These results demonstrated that similar neural mechanisms were involved in the regulation of nicotine and D-amphetamine anxiety-like behaviour in mice. The results have provided new findings to support the use of bupropion in the treatment of nicotine and/or amphetamine addiction.