BEHAVIORAL PROFILES OF THE REVERSIBLE MONOAMINE-OXIDASE-A INHIBITORS BEFLOXATONE AND MOCLOBEMIDE IN AN EXPERIMENTAL-MODEL FOR SCREENING ANXIOLYTIC AND ANTI-PANIC DRUGS

The present study compared the behavioural effects of acute and chroni c (one daily IP injection for 14 days) treatments with the reversible monoamine oxidase-A inhibitors (RIMAs) moclobemide (3 and 10 mg/kg) an d befloxatone (0.3 and 1 mg/kg) in the Mouse Defence Test Battery (MDT B) which has been designed for screening anxiolytic and anti-panic dru gs. In the MDTB, Swiss mice were confronted with a natural threat (a r at) and situations associated with this threat. Primary measures taken before, during and after rat confrontation were escape attempts, flig ht, risk assessment (RA) and defensive threat and attack. After acute administration of both compounds, no modification of defensive behavio urs were observed. This was in contrast to chronic treatments, where m oclobemide (3 and 10 mg/kg) and befloxatone (1 mg/kg) produced a signi ficant reduction in one flight measure (avoidance distance when the ra t was approaching). In addition, befloxatone (0.3 and 1 mg/kg), but no t moclobemide, increased RA responses when mice were constrained in on e part of the apparatus facing the rat, which remained at a constant d istance. No other drug effects were observed with either compound. Alt hough these behavioural profiles are consistent with an anxiolytic-lik e effect, the finding of an action upon a limited number of defence re sponses suggests a weaker anxiolytic-like potential compared to that o f classical anxiolytics. However, in view of previous data with panic- modulating compounds on flight behaviours in the MDTB, the present res ults are in line with clinical results showing that moclobemide is eff ective in panic disorders and suggest that befloxatone may have some e fficacy in the clinical management of panic.