EFFECTS OF THE 5-HT1A ANTAGONIST (-WAY-100135 ON MURINE SOCIAL AND AGONISTIC BEHAVIOR())

Compounds previously identified as 5-HT1A antagonists have subsequentl y been demonstrated to possess partial agonistic properties in models assessing somatodendritic autoreceptor function. This study examined t he influences of (+)-WAY-100135, claimed to be the first selective 5-H T1A antagonist, on offensive behaviour in male mice. Employing a resid ent-intruder paradigm, administration of (+)-WAY-100135 (1.0-10.0 mg/k g sc) enhanced elements of resident offensive behaviour at 2.5 and 5.0 mg/kg but reduced such behaviour at 10.0 mg/kg. In comparison, reside nt defensive postures remained unchanged except for a significant incr ease in defensive sideways behaviour at 10.0 mg/kg. These effects were accompanied by reduced rearing behaviour across the dose range tested . Attend/approach behaviour was significantly reduced at the lowest, b ut increased at the highest, doses tested. Such results may reflect re sponse competition rather than concomitant motor impairment. Given the dynamic behavioural interactions occurring in this paradigm, the incr eased offensive behaviour of the resident mice leads to enhanced defen ce and counter-attack by the intruder conspecifics. The results are di scussed with reference to the current literature concerning the behavi oural effects of other 5-HT1A antagonists.