<i>Htr2a</i> Expression Responds Rapidly to Environmental Stimuli in an <i>Egr3</i>-Dependent Manner

Abstract

Pharmacologic and genetic findings have implicated the serotonin 2A receptor (5-HT_2AR) in the etiology of schizophrenia. Recent studies have shown reduced 5-HT_2AR levels in schizophrenia patients, yet the cause of this difference is unknown. Environmental factors, such as stress, also influence schizophrenia risk, yet little is known about how environment may affect this receptor. To determine if acute stress alters 5-HT_2AR expression, we examined the effect of sleep deprivation on cortical <i>Htr2a</i> mRNA in mice. We found that 6 h of sleep deprivation induces a twofold increase in <i>Htr2a</i> mRNA, a more rapid effect than has been previously reported. This effect requires the immediate early gene early growth response 3 (<i>Egr3</i>), as sleep deprivation failed to induce <i>Htr2a</i> expression in <i>Egr3</i>–/– mice. These findings provide a functional link between two schizophrenia candidate genes and an explanation of how environment may influence a genetic predisposition for schizophrenia