BEHAVIORAL-EFFECTS OF PHENELZINE IN AN EXPERIMENTAL-MODEL FOR SCREENING ANXIOLYTIC AND ANTI-PANIC DRUGS - CORRELATION WITH CHANGES IN MONOAMINE-OXIDASE ACTIVITY AND MONOAMINE LEVELS

This study investigated the effects of acute and chronic tone daily i. p. injection for 14 days) treatments with the non-selective irreversib le monoamine-oxidase (MAO) inhibitor phenelzine (10 and 30 mg/kg) on d efensive behaviors of Swiss mice in the mouse defense test battery (MD TB) which has been designed for screening anxiolytic and anti-panic dr ugs. In the MDTB, subjects were confronted with a natural threat (a ra t) and situations associated with this threat. MAO-A and MAO-B activit ies and levels of brain monoamines (serotonin (5-HT), dopamine (DA) an d norepinephrine (NE)) and their deaminated metabolites were subsequen tly measured. Behavioral results showed that acute administration of p henelzine did not specifically modify defensive behaviors. By contrast , after chronic treatment, phenelzine produced a significant reduction in avoidance distance when the rat was approaching, an effect which i s consistent with an anti-panic-like action. In addition, phenelzine d isplayed weak anxiolytic-like effects as it increased risk assessment responses when mice were constrained in one part of the apparatus faci ng the rat which remained at a constant distance. No other specific dr ug effect was observed. These behavioral changes were associated with a dramatic increase in 5-HT levels, in particular after chronic treatm ent, while levels of DA and NE increased only slightly. importantly, n o significant differences in DA and NE levels between acute and chroni c regimens were observed. Levels of deaminated metabolites of monoamin es were markedly decreased. Measurements of MAO activity revealed subs tantial reductions in both type A and B forms with a full inhibition o f both forms being observed only after chronic treatment with phenelzi ne. These results suggest that the effects of phenelzine may be due ma inly to its effects on the 5-HT system and presumably related to the f ull inhibition of MAO-A and/or MAO-B. (C) 1998 Elsevier Science Ltd. A ll rights reserved.