Experimental anxiety and antidepressant drugs: the effects of moclobemide, a selective reversible MAO-A inhibitor, fluoxetine and imipramine in mice.

Abstract

Available evidence derived from behavioural and clinical studies indicates that antidepressant drugs may be effective as anxiolytic agents. In this connection, the present study was designed to assess the behavioural effects of three antidepressant drugs, i.e. imipramine (IMI), a non selective serotonin (5-HT) and noradrenaline re-uptake (NA) inhibitor, fluoxetine (FLU), a selective 5-HT re-uptake inhibitor (SSRI) and moclobemide (MOC), a reversible inhibitor of type A monoamine-oxidase enzyme (RIMA) on anxiety, exploratory and locomotor activities in mice. The experiments used two animal models which attempt to separate these three factors: the "light-dark aversion" test and the "open-field" test. Naive female CD1 mice were administered intraperitoneally (i.p.) 30 min before testing with IMI (10, 20 and 40 mg/kg) or FLU (5, 10 and 20 mg/kg) or MOC (1, 5 and 10 mg/kg) or vehicle. Results showed that IMI (10 and 20 mg/kg), FLU (10 and 20 mg/kg) and MOC (1, 5 and 10 mg/kg) significantly reduced the aversive behavior of mice for the lit area in the light/dark aversion test, suggesting an anxiolytic-like effect. In fact, vehicle controls preferred the dark box where they spent approximately 70% of their time, indicating that light serves as an anxiogenic stimulus. Importantly, the anxiolytic-like effects of these antidepressant drugs were not associated with any increase in locomotor activity. In summary, these data suggest that FLU and the new generation of RIMA, exemplified by MOC, in terms of probable efficacy and greater safety, are of interest as treatment for a broad spectrum of anxiety disorders.