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Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia
Author(s) -
Santini Martin A.,
Ratner Cecilia,
Aznar Susana,
Klein Anders B.,
Knudsen Gitte M.,
Mikkelsen Jens D.
Publication year - 2013
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23198
Subject(s) - phencyclidine , serotonin , prefrontal cortex , hallucinogen , arc (geometry) , 5 ht receptor , schizophrenia (object oriented programming) , pharmacology , agonist , receptor , psychosis , neuroscience , endocrinology , chemistry , medicine , psychology , nmda receptor , biology , psychiatry , cognition , geometry , mathematics
Prefrontal serotonin 2A receptors (5‐HT 2A Rs) have been linked to the pathogenesis and treatment of schizophrenia. Many antipsychotics fully occupy 5‐HT 2A R at clinical relevant doses, and activation of 5‐HT 2A receptors by lysergic acid diethylamide (LSD) and LSD‐like drugs induces a schizophrenia‐like psychosis in humans. Subchronic phencyclidine (PCP) administration is a well‐established model for schizophrenia‐like symptoms in rodents. The aim of the present study was to investigate whether subchronic PCP administration changes expression, binding, or functionality of cortical 5‐HT 2A Rs. As a measure of 5‐HT 2A R functionality, we used the 5‐HT 2A R agonist 2,5‐dimethoxy‐4‐iodoamphetamine (DOI)‐induced head‐twitch response (HTR) and mRNA expression of the immediate‐early genes (IEGs) activity‐related cytoskeletal associated‐protein ( Arc ), c‐fos , and early growth response protein 2 ( egr‐2 ) in the frontal cortex. Mice were treated with PCP (10 mg/kg) or saline for 10 days, followed by a 5‐day washout period. The PCP pretreatment increased the overall induction of HTR and frontal cortex IEG mRNA expression following a single challenge with DOI. These functional changes were not associated with changes in 5‐HT 2A R binding. Also, binding of the 5‐HT 1A R and the 5‐HT transporter was unaffected. Finally, basal mRNA level of Arc was increased in the prefrontal cortex after subchronic PCP administration as revealed with in situ hybridization. Together these findings indicate that PCP administration produces changes in the brain that result in an increase in the absolute effect of DOI. Therefore, neurotransmission involving the 5‐HT 2A R could contribute to the behavioral deficits observed after PCP treatment. © 2013 Wiley Periodicals, Inc.