The amplitude of the acoustic startle response is reduced by a preceding weak stimulation which by itself does not elicit the startle response. This phenomenon is named prepulse inhibition (PPI) and is thought to reflect the operation of the sensorimotor gating system, which is deficient in schizophrenic patients. It has been reported that an antagonist at the
strychnine-insensitive
glycine site has atypical
neuroleptic properties in experimental animals. To evaluate the effect of an antagonist at the site on disrupted PPI, we examined whether (+)-
HA-966 antagonizes
phencyclidine-induced (3 mg/kg s.c.) and
apomorphine-induced (1 mg/kg s.c.) disruption of PPI in rats. In addition, its effect on
phencyclidine-induced hyperactivity was tested. The effects of (+)-
HA-966 were compared with those of
haloperidol, a typical
neuroleptic. (+)-
HA-966 antagonized
phencyclidine-induced hyperactivity, but not
phencyclidine-induced disruption of PPI, which is thought to be a model of refractory symptoms in
schizophrenia. Furthermore, (+)-
HA-966 did not improve the deficit in PPI induced by
apomorphine. On the other hand,
haloperidol antagonized
phencyclidine-induced hyperactivity and the disruption of PPI by
apomorphine, but not by
phencyclidine. The results of this study might mean that (+)-
HA-966 antagonizes the behavioral change induced by excessive
dopamine release (the increment of locomotor activity due to
phencyclidine), but not the effect induced by a direct
dopamine agonist or the
dopamine-independent effect of
phencyclidine (the disruption of PPI). Thus, as regards antagonism of
phencyclidine-induced disruption of PPI, (+)-
HA-966 does not appear to have an atypical
neuroleptic-like effect.