GENETICS, HALOPERIDOL-INDUCED CATALEPSY AND HALOPERIDOL-INDUCED CHANGES IN ACOUSTIC STARTLE AND PREPULSE INHIBITION

The acoustic startle response (ASR), prepulse inhibition (PPI) of the ASR and the effects of haloperidol on the ASR and PPI were examined in C57BL/6J (B6) and DBA/2 (D2) inbred mouse strains and their F-1 and F -2 progeny. The startle stimulus was a 60-ms, 110-dB, 10-kHz tone; the prepulse stimuli were 20-ms white noise bursts at 56, 68 and 80 dB ag ainst a 50-dB background presented 100-ms before the startle pulse. Th e B6 strain showed modest PPI (25-40%); in contrast, the D2 strain sho wed on average no PPI and numerous individuals showed prepulse augment ation (PPA). The F-2 progeny showed an intermediate PPI; however, the extreme values ranged from 200% PPA to essentially 100% PPI. Haloperid ol in dose-dependent fashion, increased PPI in both the B6 and D2 stra ins; the threshold dose was in the range of 0.1-0.2 mg/kg. Raclopride (0.3 mg/kg), clozapine (2 mg/kg) and risperidone (0.4 mg/kg) also incr eased PPI in both strains. The effects of haloperidol (0.4 mg/kg) on P PI in 140 F-2 progeny were examined. For all prepulse intensities, the re were highly significant (r > 0.80) and negative correlations betwee n baseline PPI and the haloperidol-induced change in PPI. Thus, those animals that showed the greatest PPA showed the greatest haloperidol-i nduced increase in PPI. There was, however, significant variance in th e haloperidol response; plots of the regression residuals showed the m ost and least responsive animals differed by almost 100% in effect on PPI. The F-2 progeny were subsequently phenotyped for haloperidol-indu ced catalepsy. There was no association between the variation in effec ts on catalepsy and PPI. However, it was observed that those individua ls with the poorest baseline PPI were catalepsy non-responsive.