Behavioural profiles of the reversible monoamine-oxidase-A inhibitors befloxatone and moclobemide in an experimental model for screening anxiolytic and anti-panic drugs

Abstract

The present study compared the behavioural effects of acute and chronic (one daily IP injection for 14 days) treatments with the reversible monoamine oxidase-A inhibitors (RIMAs) moclobemide (3 and 10 mg/kg) and befloxatone (0.3 and 1 mg/kg) in the Mouse Defence Test Battery (MDTB) which has been designed for screening anxiolytic and anti-panic drugs. In the MDTB, Swiss mice were confronted with a natural threat (a rat) and situations associated with this threat. Primary measures taken before, during and after rat confrontation were escape attempts, flight, risk assessment (RA) and defensive threat and attack. After acute administration of both compounds, no modification of defensive behaviours were observed. This was in contrast to chronic treatments, where moclobemide (3 and 10 mg/kg) and befloxatone (1 mg/kg) produced a significant reduction in one flight measure (avoidance distance when the rat was approaching). In addition, befloxatone (0.3 and 1 mg/kg), but not moclobemide, increased RA responses when mice were constrained in one part of the apparatus facing the rat, which remained at a constant distance. No other drug effects were observed with either compound. Although these behavioural profiles are consistent with an anxiolytic-like effect, the finding of an action upon a limited number of defence responses suggests a weaker anxiolytic-like potential compared to that of classical anxiolytics. However, in view of previous data with panic-modulating compounds on flight behaviours in the MDTB, the present results are in line with clinical results showing that moclobemide is effective in panic disorders and suggest that befloxatone may have some efficacy in the clinical management of panic.