SOME, BUT NOT ALL, ANTIPSYCHOTIC-DRUGS POTENTIATE A LOW-LEVEL OF PREPULSE INHIBITION SHOWN BY RATS OF THE WISTAR STRAIN

In a previous study using Sprague-Dawley rats, we showed that in a pre pulse inhibition (PPI) procedure with levels of PPI ranging from appro ximately 10 to 40% (for prepulse intensities 2, 9 and 15 dB above back ground noise), the antipsychotics clozapine and haloperidol, hut also the alpha(1) adrenoceptor antagonist prazosin, robustly and dose-depen dently potentiated PPI. In contrast, the antipsychotics risperidone, a misulpride, raclopride and remoxipride did not potentiate PPI. The fal se positive (prazosin) and the four false negatives led us to conclude that this PPI-enhancing procedure lead poor predictive validity as a screening tool for potential antipsychotics. In the present study, we used Wistar rats, which under the same protocol as that used far Sprag ue-Dawley rats show a very low level of PPI. We examined the ability o f six antipsychotics, given intraperitoneally (i.p.), to reverse this PPI deficit. It was found that clozapine (5-20 mg/kg), olanzapine (5-2 0 mg/kg) and sertindole (1-10 mg/kg) reversed this deficiency of PPI ( i.e. potentiated the low level of PPI). In contrast, risperidone (0.1- 1 mg/kg), remoxipride (1-10 mg/kg) and haloperidol (0.1-1 mg/kg) were inactive. The negative results with three clinically active antipsycho tics (risperidone, remoxipride and haloperidol) indicate that reversal of this PPI deficit in Wistar rats has poor predictive validity to sc reen for potential antipsychotic activity. In an attempt to investigat e the mechanism that might underlie the reversing effect of clozapine, olanzapine and sertindole, we tested the ability of the alpha(1) adre noceptor antagonist prazosin (3-20 mg/kg), the dopamine D-1 receptor a ntagonist SCH 23390 (0.01-0.1 mg/kg) and the 5-HT2 antagonist ritanser in (0.3-3 mg/kg) to reverse the PPI deficit. Negative results with the se threat drugs did not allow us to characterize the receptor(s) that might be implicated in the reversal of this type of PPI deficit.