The effects of moclobemide on the yohimbine-induced anxiogenic action in the elevated plus-maze

Abstract

Moclobemide (MOC), a selective and reversible MAO-A inhibitor, was claimed to have both anxiolytic and anxiogenic properties. Therefore, we assessed whether: (1) acute and subchronic (10 days) MOC treatments, in doses which display antidepressant activity, affect the performance of rats in the elevated plus-maze that provides detection of both anxiolytic and anxiogenic properties in the same experimental conditions; (2) the alpha(2) antagonist yohimbine (YOH), which increases noradrenaline (NA) release, is able to modify the effects of MOC treatments in the elevated plus-maze. The results showed that MOC, at doses of 10 and 20 mg kg(-1) i.p. either acutely or subchronically administered, significantly reduced the immobility time in the forced swimming test in rats. In other words, it displayed antidepressant activity. In the elevated plus-maze, acutely administered MOC (20 mg kg(-1) i.p.) significantly increased both the percentage of open arm entries and the time spent in open arms, while only the former parameter was increased in response to 10 mg kg(-1) i.p. MOC treatment. Thus, the anxiolytic action of MOC at a dose of 20 mg kg(-1) i.p. was more prominent. Subchronically administered MOC at both doses significantly increased the two parameters. Hence, it can be stated that anxiolytic action of subchronically administered MOC appears to be more pronounced. Acutely administered YOH (0.5 mg kg(-1) i.p.) showed anxiogenic effect in the elevated plus-maze. However, in both acutely and subchronically MOC-treated animals, YOH failed to exert its anxiogenic effect. This implies the importance of NA-gic activity in the MOC-induced anxiolytic action. (C) 1998 The Italian Pharmacological Society.