ABSTRACT
The development of specific 5–HT3 antagonists with high receptor affinity has recently led to the discovery that such drugs are involved in the modulation of anxiety, psychosis and aggression. Costall et al (1987) and Tyers (1988) have described significant efficacy of 5–HT3 antagonists on the behaviour of animals in models thought to be predictive for anxiolytic and antipsychotic activity. Part of their evidence is based on a model of dopamine infusion in the nucleus accumbens. Since this is neither a simple model nor generally used, we tried to replicate the effects of two 5–HT3–antagonists, GR38032F and MDL 72222, in two more routinely used animal models of antipsychotic activity, conditioned avoidance response (CAR) and (functional) antagonism of dopaminergic behaviour, apomorphine–induced climbing. As anxiolytic tests we used the four–plate test, the light/dark exploration model and a recently developed model for separation–induced anxiety–ultrasonic calling of rat pups. Because of our interest in the role of serotonin in aggression we also investigated 5–HT3 antagonists in aggression; as models we used isolation–induced aggression in mice and maternal aggression in lactating female rats. For comparative reasons, we used the reference compounds haloperidol (neuroleptic), diazepam (anxiolytic) and eltoprazine (serenic).
