Clozapine and PD149163 elevate prepulse inhibition in Brown Norway rats

Abstract

Unmedicated schizophrenia patients exhibit deficits in prepulse inhibition (PPI) of the acoustic startle response. Similar deficits can be induced in rodents via a variety of manipulations and these deficits can be reversed by antipsychotics. Brown Norway (BN) rats exhibit natural PPI deficits under certain parametric conditions. We treated BN rats with haloperidol or clozapine to determine if the BN rat is a useful animal model with predictive validity for the effects of antipsychotics. In addition, we also tested PD149163, a neurotensin-1 receptor agonist, which has been shown to exhibit antipsychotic-like effects in several other animal models. BN rats received subcutaneous injections of either saline or one of two doses of haloperidol (0.5 mg/kg, 1.0 mg/kg), clozapine (7.5 mg/kg, 10 mg/kg) or PD149163 (1.0 mg/kg, 2.0 mg/kg). PPI was measured in startle chambers 30 min after injection. Systemic clozapine and PD149163 but not haloperidol facilitated PPI in BN rats (p < .001). This drug response profile suggests that the BN rat may be useful for detecting atypical antipsychotics and antipsychotics with novel mechanisms of action. The results also add to the evidence suggesting that PD149163 may have antipsychotic properties.

Figure 1

The effect of haloperidol, clozapine, and PD149163 administration on PPI (Main) and startle magnitude (Inset). Doses are mg/kg. Significantly different from saline treated represented by **P < 0.01. Data displayed as the mean±SEM.