The effects of subchronic haloperidol on intact and dizocilpine-disrupted sensorimotor gating

Rationale: Reversal of deficits in prepulse inhibition (PPI) of the startle reflex in rats is considered a preclinical screen for potential antipsycho tics, Whereas acutely administered antipsychotics consistently reverse apom orphine-induced deficits in PPI, some antipsychotics, including haloperidol , are unable to reverse deficits in PPI produced by non-competitive NMDA an tagonists such as phencyclidine or dizocilpine (MK-801). Acute administrati on of antipsychotics tends to facilitate baseline PPI. However, the effect is generally not large enough in magnitude nor reliable enough to be consid ered a useful preclinical screen for antipsychotic activity. Objective: Bec ause the clinical effects of antipsychotics typically require subchronic ad ministration, this study tested the hypothesis that reversal of NMDA antago nist-induced deficits in PPI by antipsychotics require subchronic administr ation. A second aim of this study was to determine if subchronic administra tion of an antipsychotic produces a more potent facilitation of baseline PP I than acute administration. Methods: Rats received a subcutaneous injectio n of 0, 0.025, 0.1 or 0.5 mg/kg haloperidol for 16 consecutive days. On day 16, half the rats in each haloperidol dose group received a second subcuta neous injection consisting of either dizocilpine (0.1 mg/kg) or saline. Res ults: None of the haloperidol doses tested had a significant effect on base line PPI. The 0.1 mg/kg dose of haloperidol diminished but did not complete ly reverse dizocilpine-induced disruption of PPI. The other doses had no si gnificant effect. Conclusions: These results suggest that time course facto rs may partially modify the effects of haloperidol on dizocilpine-induced d isruption of PPI but not its effect on baseline PPI.