The effects of M100907 in pharmacological and developmental animal models of prepulse inhibition deficits in schizophrenia

Patients with schizophrenia exhibit deficits in an operational measure of s ensorimotor gating: prepulse inhibition (PPI) of the startle response. M100 907, a selective 5-HT2A-receptor antagonist that has been developed for cli nical testing as nit antipsychotic in schizophrenic patients, has been test ed in several animal models of the gating deficits in schizophrenia, includ ing PPI. Previous studies have shown that M100907 blacks or reduces the dis ruptive effects of hallucinogenic 5-HT2 agonists (e.g., DOI) and psychotomi metic NMDA antagonists (e.g., phencyclidine) on PPI. In the present payer, toe report the results of three studies conducted to determine the effects of M100907 on apomorphine-induced disruption (one experiment) and isolation rearing-induced disruption of PPI in rats (two experiments). Results showe d that M100907 failed to reduce the disruption of PPI caused by the dopamin e agonist agonist apomorphine. Nevertheless, M100907 partially reduced the disruption of PPI caused by isolation rearing. Thus, M100907 shows efficacy as a putative antipsychotic in nondopaminergic PPI models of the sensorimo tor gating deficits in schizophrenia. [Neuropsychopharmacology 21:S134-S142 , 1999] (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.