Chronic treatment with haloperidol diminishes the phencyclidine-induced sensorimotor gating deficit in rats

Prepulse inhibition is a model in which a weak subthreshold stimulus (prepulse), presented to an individual before a strong stimulus (pulse), inhibits a startle response to the latter. A deficit of prepulse inhibition induced by dopaminomimetics and antagonists of NMDA receptors has been suggested as an animal model of the sensorimotor deficit in schizophrenia. The aim of the present study was to examine the effect of chronic treatment with the classic neuroleptic haloperidol on the disruption of prepulse inhibition induced by the uncompetitive antagonist of NMDA receptors phencyclidine (PCP, 5 mg/kg sc). Haloperidol in a dose of 1 mg/kg/day was given to rats in drinking water for 3 months. The PCP-induced reduction in prepulse inhibition was not reversed by short-term (4-day) haloperidol administration. In contrast, long-term treatment with haloperidol (6 weeks or 3 months) diminished the PCP-induced effect. The present study suggests that the improvement in sensorimotor gating in the PCP model in rats by prolonged treatment with haloperidol may reflect its antipsychotic action.