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, 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 alpha-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 alpha-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.
Yamada
S
S
Institute of Brain Diseases, Kurume University School of Medicine, Japan.
Harano
M
M
Annoh
N
N
Nakamura
K
K
Tanaka
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D001307:Auditory Perception / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects*
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D011985:Receptors, Serotonin; D010622:Phencyclidine; D001058:Apomorphine