DIFFERENTIAL-EFFECTS OF THE STRYCHNINE-INSENSITIVE GLYCINE SITE ANTAGONIST (-HA-966 ON THE HYPERACTIVITY AND THE DISRUPTION OF PREPULSE INHIBITION INDUCED BY PHENCYCLIDINE IN RATS())

The amplitude of the acoustic startle response is reduced by a precedi ng weak stimulation which by itself does not elicit the startle respon se. This phenomenon is named prepulse inhibition (PPI) and is thought to reflect the operation of the sensorimotor gating system, which is d eficient in schizophrenic patients. It has been reported that an antag onist at the strychnine-insensitive glycine site has atypical neurolep tic properties in experimental animals. To evaluate the effect of an a ntagonist at the site on disrupted PPI, we examined whether (+)-HA-966 antagonizes phencyclidine-induced (3 mg/kg s.c.) and apomorphine-indu ced (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 p hencyclidine-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 ha nd, haloperidol antagonized phencyclidine-induced hyperactivity and th e disruption of PPI by apomorphine, but not by phencyclidine. The resu lts of this study might mean that (+)-HA-966 antagonizes the behaviora l change induced by excessive dopamine release (the increment of locom otor activity due to phencyclidine), but not the effect induced by a d irect dopamine agonist or the dopamine-independent effect of phencycli dine (the disruption of PPI). Thus, as regards antagonism of phencycli dine-induced disruption of PPI, (+)-HA-966 does not appear to have an atypical neuroleptic-like effect. (C) 1998 Elsevier Science B.V.