Early emergence of altered 5-HT2A receptor-evoked behavior, neural activation and gene expression following maternal separation.

The early stress of Maternal Separation (MS) contributes to the establishment of adult psychopathology. The serotonergic (5-HT) system is implicated during this temporal window in mediating the development of mood-related behaviors. MS is reported to evoke altered 5-HT 2A receptor function in adulthood. However, the ontogeny of altered 5-HT 2A receptor responsivity following MS remains unknown. Here, we examined 5-HT 2A receptor agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) (2 mg/kg) evoked responses, namely stereotypical head-twitch behaviors in control and MS Sprague-Dawley rat pups at postnatal day 21 (P21). MS involved a separation of pups from the dam for 3 h daily from postnatal day 2–14. MS pups at P21 exhibited significantly enhanced head-twitch behaviors compared to controls. Using c-Fos cell counting we examined neural activation in control and MS pups following DOI treatment. MS pups exhibited altered DOI-evoked c-Fos expression within all mPFC subdivisions, but not in the hippocampus, lateral septum and hypothalamus, suggesting differential prefrontal neural activation upon 5-HT 2A receptor stimulation following early stress. Gene profiling of 5-HT 2A receptor-regulated immediate early genes (IEGs) indicated a decline in the expression of Fos , Fra1 and Egr1 mRNA under baseline conditions in the mPFC of MS pups. MS pups also showed an altered pattern in the regulation of several 5-HT 2A receptor-regulated IEGs ( Fos , Fra1 , Bdnf , Egr1 , Egr3 ) following DOI treatment. Collectively, these results highlight an early emergence of altered 5-HT 2A receptor-evoked behavioral responses and neural activation patterns in multiple brain regions in animals with a history of MS. [ABSTRACT FROM AUTHOR]