Enhanced Function of Prefrontal Serotonin 5-HT2 Receptors in a Rat Model of Psychiatric Vulnerability

摘要: Prefrontal serotonin 5-HT2 receptors have been linked to the pathogenesis and treatment of affective disorders, yet their function in psychiatric vulnerability is not known. Here, we examine effects a rat model using electrophysiology, gene expression, behavior. Following early stress chronic maternal separation, found that has atypical receptor-mediated excitatory adult prefrontal cortex were blocked by 5-HT2A receptor antagonist MDL 100907. In absence serotonergic agonist, intrinsic excitability was enhanced relative controls. Yet, response stimulation receptors, animals with history exhibit heightened network activity vitro, immediate expression vivo, potentiated head shake These changes arise any major alteration 5-HT2A/C mRNA or binding. Our microarray results quantitative PCR validation provide insight into molecular accompany such following stress. We observed persistent transcriptome changes, significant enrichment genes involved cellular developmental processes, regulation signal transduction, G-protein signaling. Specific regulated validated an independent cohort, several altered normalized blockade adulthood. Together, our demonstrate alterations vulnerability.