Effects of the 5-HT1A antagonist (+)-WAY-100135 on murine social and agonistic behavior

Compounds previously identified as 5-HT1A antagonists have subsequently been demonstrated to possess partial agonistic properties in models assessing somatodendritic autoreceptor function. This study examined the influences of (+)-WAY-100135, claimed to be the first selective 5-HT1A antagonist, on offensive behaviour in male mice. Employing a resident-intruder paradigm, administration of (+)-WAY-100135 (1.0-10.0 mg/kg s.c.) 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, resident defensive postures remained unchanged except for a significant increase 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, but increased at the highest, doses tested. Such results may reflect response competition rather than concomitant motor impairment. Given the dynamic behavioural interactions occurring in this paradigm, the increased offensive behaviour of the resident mice leads to enhanced defence and counter-attack by the intruder conspecifics. The results are discussed with reference to the current literature concerning the behavioural effects of other 5-HT1A antagonists.