title: Activation of 5-HT1Areceptors in the rat dorsomedial hypothalamus inhibits stress-induced activation of the hypothalamic-pituitary-adrenal axis.
abstract: Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to the release of corticosteroid hormones into the circulation, is an adaptive response to perceived threats. Persistent activation of the HPA axis can lead to impaired physiological or behavioral function with maladaptive consequences. Thus, efficient control and termination of stress responses is essential for well-being. However, inhibitory control mechanisms governing the HPA axis are poorly understood. Previous studies suggest that serotonergic systems, acting within the medial hypothalamus, play an important role in inhibitory control of stress-induced HPA axis activity. To test this hypothesis, we surgically implanted chronic jugular cannulae in adult male rats and conducted bilateral microinjection of vehicle or the 5-HT1Areceptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT; 8 nmol, 0.2 μL, 0.1 μL/min, per side) into the dorsomedial hypothalamus (DMH) immediately prior to a 40 min period of restraint stress. Repeated blood sampling was conducted using an automated blood sampling system and plasma corticosterone concentrations were determined using enzyme-linked immunosorbent assay. Bilateral intra-DMH microinjections of 8-OH-DPAT suppressed stress-induced increases in plasma corticosterone within 10 min of the onset of handling prior to restraint and, as measured by area-under-the-curve analysis of plasma corticosterone concentrations, during the 40 min period of restraint. These data support an inhibitory role for serotonergic systems, acting within the DMH, on stress-induced activation of the HPA axis. Lay summary: Inhibitory control of the hypothalamic-pituitary-adrenal (HPA) stress hormone response is important for well-being. One neurochemical implicated in inhibitory control of the HPA axis is serotonin. In this study we show that activation of serotonin receptors, specifically inhibitory 5-HT1Areceptors in the dorsomedial hypothalamus, is sufficient to inhibit stress-induced HPA axis activity in rats.
authors.affiliation: a Department of Integrative Physiology and Center for Neuroscience , University of Colorado Boulder , Boulder , CO , USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Stamper
authors.affiliation: a Department of Integrative Physiology and Center for Neuroscience , University of Colorado Boulder , Boulder , CO , USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Hassell
authors.affiliation: a Department of Integrative Physiology and Center for Neuroscience , University of Colorado Boulder , Boulder , CO , USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Kapitz
authors.affiliation: b Department of Biology , University of South Dakota , Vermillion , SD , USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Renner
authors.affiliation: c School of Life Sciences, Arizona State University , Tempe , AZ , USA.
authors.forename: Miles
authors.initials: M
authors.lastname: Orchinik
authors.affiliation: a Department of Integrative Physiology and Center for Neuroscience , University of Colorado Boulder , Boulder , CO , USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D007031:Hypothalamus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone
keywords: 5-HT1A; HPA axis; corticosterone; dorsomedial hypothalamus; negative feedback; serotonin