POTENTIATION OF THE TIME-DEPENDENT, ANTIDEPRESSANT-INDUCED CHANGES INTHE AGONISTIC BEHAVIOR OF RESIDENT RATS BY THE 5-HT1A RECEPTOR ANTAGONIST, WAY-100635

Acute and chronic antidepressant drug treatments respectively decrease and increase the aggressive behaviour of resident rats during encount ers with unfamiliar conspecifies. We have now examined the effect of t he 5-hydroxytryptamine(1A) receptor antagonist, WAY-100635, on fluoxet ine-, paroxetine- or venlafaxine-induced changes in aggression. WAY-10 0635 (0.1 mg/kg), which did not modify behaviour when given alone, pot entiated the venlafaxine (5.54 mg/kg)-induced reduction in aggression after acute treatment and, during chronic treatment, accelerated the f luoxetine (0.34 mg/kg/day)-induced increase in aggression, from day 5 to day 2. A similar change in time course was seen with paroxetine (0. 33 mg/kg/day), although the increase in aggression was smaller. Venlaf axine (5.54 mg/kg/day, alone or co-administered with WAY-100635) incre ased aggression by day 2. During chronic treatment, therefore, venlafa xine, at the dose used, had a more rapid onset of action than either f luoxetine or paroxetine, whereas the fluoxetine- and paroxetine-, but not the venlafaxine-, induced increase in aggression was accelerated b y WAY-100635. These studies further support the hypothesis that select ive blockade of the 5-hydroxytryptamine(1A) receptor augments the effe cts of antidepressant drugs in an animal model predictive of antidepre ssant activity, presumably by concomitant blockade of the somatodendri tic 5-hydroxytryptamine(1A) autoreceptor-mediated negative feedback sy stem of serotonergic neurones.