Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia.
Journal of Neuroscience Research May 1, 2013 Martin A. Santini, Cecilia Ratner, Susana Aznar et al.
Subchronic administration of phencyclidine (PCP) to mice increases the sensitivity of serotonin 2A receptors (5-HT2A Rs) in the frontal cortex. Mice treated with PCP (10 mg/kg) for 10 days, followed by a 5-day washout, showed a stronger head-twitch response and greater expression of immediate-early genes (Arc, c-fos, egr-2) after a challenge with the 5-HT2A R agonist DOI, compared to saline-treated mice. These functional changes occurred without alterations in 5-HT2A R binding or in binding of the 5-HT1A receptor or serotonin transporter. Basal Arc mRNA levels were also elevated in the prefrontal cortex. The findings suggest that PCP-induced changes enhance 5-HT2A R-mediated neurotransmission, which may contribute to behavioral deficits in this schizophrenia model.