CHRONIC ADMINISTRATION OF THE 5-HT3 RECEPTOR ANTAGONIST BRL-43694 - EFFECTS ON REFLEX EPILEPSY AND SOCIAL-BEHAVIOR OF THE MONGOLIAN GERBIL

The 5-HT3 receptor antagonist BRL 43694 was administered in drinking fluid to Mongolian gerbils, previously selected for their propensity to exhibit seizures on mild stimulation, for 11 days at doses of 1.5 μg/kg, 150 μg/kg and 1 mg/kg daily, while controls received tap water. Effects upon behaviour during encounters under white light with an untreated resident gerbil were assessed using ethological procedures. Effects upon seizure susceptibility and severity were also examined. All doses of BRL 43694 significantly increased the time spent by gerbils in the social activity "attend", and acts of social investigation involving physical contact between animals were significantly increased only by the highest dose of 1 mg/kg, as was occurrence of the specific element, "groom". The duration of flight was increased in gerbils receiving the drugs at 1.5 μg/kg. The treatment had no effect upon seizure susceptibility or severity. It is suggested that BRL 43694 increases the sensitivity of gerbils to their social environment. At the lower dose this was seen as an increase in flight, at all doses it was associated with increase of the social activity "attend" and at the high dose it was manifested as an increase in active social interaction. Further investigations are required to assess the relevance of these findings to the purported anxiolytic activity of 5-HT3 receptor antagonists. © 1990 Springer-Verlag.