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, the mechanism underlying this disruption remains unclear. The present experiment tested the hypothesis that serotonin 2A receptor blocking property of drugs reverses the phencyclidine-induced PPI disruption.
Methods: The ED50 value of spiperone, haloperidol, chlorpromazine, clozapine, risperidone, olanzapine, seroquel, pipamperone, mianserin, or desipramine to reverse the phencyclidine- or apomorphine-induced PPI disruption in rats was determined. Then the correlation between the ED50 value and the affinity for the serotonin 2A, 2C, dopamine D2, or α-1 receptor of each drug was examined.
Results: The ED50 value of the drugs to reverse the phencyclidine-induced PPI disruption was significantly correlated with the affinity for the serotonin 2A receptor, but not for the dopamine D2, serotonin 2C, or α-1 receptor of each drug. In contrast, the ED50 value of the drugs to reverse the apomorphine-induced PPI disruption was significantly correlated with the affinity for the dopamine D2 receptor, but not for the serotonin 2A receptor.
Conclusions: An activation of serotonin 2A receptors would mediate the phencyclidine-induced PPI disruption.
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- Phencyclidine-induced deficits in prepulse inhibition of startle are blocked by prazosin, an α-1 noradrenergic antagonist.J Pharmacol Exp Ther. 1997; 283: 666-674
- Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic olanzapine.Psychopharmacology. 1995; 122: 198-201
- Clozapine antagonizes phencyclidine-induced deficits in sensorymotor gating of the startle response.J Pharm Exp Ther. 1994; 271: 787-794
- Prestimulus effects on human startle reflex in normals and schizophrenics.Psychophysiology. 1978; 15: 339-343
- Radioreveptor binding profile of the atypical antipsychotic olanzapine.Neuropsychopharmacology. 1996; 14: 87-96
- Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin subtype selective antagonists in mice.Psychopharmacology. 1997; 129: 79-84
- The more or less startling effects of weak prestimulation.Psychophysiology. 1975; 12: 238-248
- Phencyclidine (PCP) injected in the nucleus accumbens increases extracellular dopamine and serotonin as measured by microdialysis.Life Sci. 1988; 42: 1713-1723
- The effects of haloperidol and clozapine on the disruption of sensorimotor gating induced by the noncompetitive glutamate antagonist MK-801.Psychopharmacology. 1993; 111: 339-344
- Effects of phencyclidine metabolites on serotonin uptake in rat brain.Neurosci Lett. 1996; 209: 153-156
- Prepulse inhibition of acoustic startle, a measure of sensorimotor gating.Pharmacol Biochem Behav. 1995; 52: 649-654
- Failure of haloperidol to block the effects of phencyclidine and dizocilpine on prepulse inhibition of startle.Biol Psychiatry. 1991; 30: 557-566
- Ventral pallidal GABA-A receptors regulate prepulse inhibition of acoustic startle.Brain Res. 1995; 684: 26-35
- m-chlorophenylpiperadine (MCPP) effects in neuroleptic-free schizophrenic patients.Arch Gen Psychiatry. 1993; 50: 624-635
- (3H)-ketanserin (R 41 468), a selective 3H-ligand for serotonin2 receptor binding sites.Mol Pharmacol. 1982; 21: 301-314
- Systemic phencyclidine administration is associated with increased dopamine, GABA and 5-HIAA levels in the dorsolateral striatum of conscious rats.J Neural Transm Gen Sect. 1994; 95: 145-155
- Neonatal excitotoxic hippocampal damage in rats caused post-pubertal changes in prepulse inhibition of startle and its disruption by apomorphine.Psychopharmacology. 1995; 122: 35-43
- The N-methyl-d-aspartate receptor antagonist MK-801 induces increases in dopamine and serotonin metabolism in several brain regions of rats.Neurosci Lett. 1991; 128: 191-194
- Adverse effects of fenfluramine in treatment refractory schizophrenia.J Clin Psychopharmacol. 1989; 9: 110-115
- Blockade of phencyclidine-induced hyperlocomotion by clozapine and MDL 100,907 in rats reflects antagonism of 5-HT2A receptors.Eur J Pharmacol. 1995; 280: R9-R11
- Phencyclidine-induced head-twitch response as 5-HT2 receptor-mediated behavior in rats.Neurosci Lett. 1987; 76: 335-338
- Serotonergic involvement in phencyclidine-induced behaviors.Pharmacol Biochem Behav. 1984; 21: 401-408
- Presynaptic activation of the spinal resotonergic system in the rat by phencyclidine.J Pharm Exp Ther. 1989; 250: 177-183
- Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency.Am J Psychiatry. 1980; 137: 1518-1522
- The role of serotonin in schizophrenia.in: Bloom F.E Kupfer D.J Psychopharmacology, The Fourth Generation of Progress. Raven Press, New York1995: 1215-1227
- Dopamine receptors, clinical correlates.in: Bloom F.E Kupfer D.J Psychopharmacology, The Fourth Generation of Progress. Raven Press, New York1995: 295-302
- Multiple serotonin receptor subtypes modulate prepulse inhibition of the startle response in rats.Neuropharmacology. 1994; 33: 441-448
- DOI disrupts prepulse inhibition of startle in rats via 5-HT2A receptors in the ventral pallidum.Brain Res. 1997; 761: 97-104
- Seroquel restores sensorimotor gating in phencyclidine-treated rats.J Pharmacol Exp Ther. 1996; 279: 1290-1299
- Assesing the validity of an animal model of deficit sensorimotor gating in schizophrenic patients.Arch Gen Psychiatry. 1994; 51: 139-154
- Effect of spiperone, raclopride, SCH23390 and clozapine on apomorphine inhibition of sensorimotor gating of the startle response in the rat.J Pharmacol Exp Ther. 1991; 256: 530-536
- Reversal of dizocilpine-induced disruption of prepulse inhibition of an acoustic startle response by the 5-HT 2 receptor antagonist ketanserin.Eur J Pharmacol. 1995; 287: 201-205
- Examination of drug-induced and isolation-induced disruption of prepulse inhibition as models to screen antipsychotic drugs.Psychopharmacology. 1995; 122: 15-26
- Presynaptic dopamine-glutamate interaction in the nucleus accumbens regulate sensorimotor gating.Psychopharmacology. 1995; 120: 433-441
- Dopamine autoreceptors in rat nucleus accumbens modulate prepulse inhibition of acoustic startle.Pharmacol Biochem Behav. 1998; 60: 803-808
- Phencyclidine-induced head-weaving and head-twitch through interaction with 5-HT1 and 5-HT2 receptors in reserpinized rats.Neuropharmacology. 1987; 26: 1489-1497
Accepted: November 2, 1998
Received in revised form: October 20, 1998
Received: March 16, 1998
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.