THE EFFECTS OF HALOPERIDOL AND CLOZAPINE ON THE DISRUPTION OF SENSORIMOTOR GATING INDUCED BY THE NONCOMPETITIVE GLUTAMATE ANTAGONIST MK-801

The amplitude of the acoustic startle response in rats is decreased if the startle stimulus is preceded by a nonstartle-eliciting auditory s timulus. This sensory gating phenomenon, known as prepulse inhibition, is diminished in schizophrenic individuals. In rats, the noncompetiti ve glutamate antagonist MK-801 disrupts prepulse inhibition. The prese nt study examined whether the disruption by MK-801 is reversible in ra ts pretreated with the classical antipsychotic haloperidol or the atyp ical antipsychotic clozapine. Male Sprague-Dawley rats were placed int o a startle chamber and presented with auditory stimuli consisting of either 95 or 105 dB tones presented alone or preceded by a 70 dB tone. Rats treated with 0.1 mg/kg MK-801 demonstrated a significant disrupt ion of prepulse inhibition. Haloperidol (0.1 and 0.5 mg/kg) and clozap ine (1.0 and 5.0 mg/kg) each consistently failed to antagonize the MK- 801-induced blockade of prepulse inhibition. The effects of haloperido l and clozapine on prepulse inhibition were also examined in saline-tr eated rats. Clozapine and, to some extent, haloperidol produced a dose -related facilitation of prepulse inhibition. Although preliminary, th is finding raises the possibility that the enhancement of prepulse inh ibition by antipsychotics might provide a useful rodent model for scre ening potential antipsychotic drugs.