Involvement of serotonin 2A receptors in phencyclidine-induced disruption of prepulse inhibition of the acoustic startle in rats

Background: The disruption of prepulse inhibition of acoustic startle (PPI) is an animal model for some aspects of schizophrenia. Phencyclidine causes psychotomimetic symptoms in human and disrupts PPI in animals, however, th e mechanism underlying this disruption remains unclear The present experime nt tested the hypothesis that serotonin 2A receptor blocking property of dr ugs reverses the phencyclidine-induced PPI disruption. Methods: The ED50 value of spiperone, haloperidol, chlorpyomazine, clozapin e, risperidone, olanzapine, seroquel, pipamperone, mianserin, or desipramin e to reverse the phencyclidine- or apomorphine-induced PPI disruption in ra ts was determined Then the correlation between the ED50 value and the affin ity for the serotonin 2A, 2C, dopamine D-2, or alpha-1 receptor of each dru g was examined. Results: The ED50 value of the drugs to reverse the phencyclidine-induced P PI disruption was significantly correlated with the affinity for the seroto nin 2A receptor, but not for the dopamine D-2, serotonin 2C, or alpha-1 rec eptor of each drug. In contrast, the ED50 value of the drugs to reverse the apomorphine-induced PPI disruption was significantly correlated with the a ffinity for the dopamine D-2 receptor, but not for the serotonin 2A recepto r Conclusions: An activation of serotonin 2A receptors would mediate the phen cyclidine-induced PPI disruption. (C) 1999 Society of Biological Psychiatry .