5-HT1A receptor agonist flesinoxan enhances Fos immunoreactivity in rat central amygdala, bed nucleus of the stria terminalis and hypothalamus
Abstract
5-Hydroxytryptamine-1A (5-HT1A) receptor agonists, including flesinoxan, reduce anxiety and activate the hypothalamus-pituitary-adrenal (HPA) axis under basal conditions. In order to investigate the underlying neural mechanisms we investigated immunoreactivity for the immediate early gene protein product Fos (Fos-ir) in rat brains 1 h after flesinoxan treatment (0.0, 0.3 or 3.0 mg/kg p.o.). Typically, 5-HT1A receptor-containing brain areas, such as the dorsal raphe nuclei, hippocampus, septum, diagonal band and the cortical and basomedial amygdala, do not show Fos-ir. Apparently, binding of flesinoxan at the 5-HT1A receptor does not directly lead to activation of c-fos in the cell, probably due to its negative coupling to adenylate cyclase. However, in typically non-5HT1A receptor-containing brain areas Fos-ir is increased due to flesinoxan treatment, as in the paraventricular nucleus of the hypothalamus (PVN), the dorsolateral part of the bed nucleus of the stria terminalis (BNSTdl) and the central amygdala (CeA). Flesinoxan-treated rats also exhibited higher plasma corticosterone levels than vehicle-treated animals, which suggests the involvement of corticotropin-releasing hormone (CRH) or vasopressin in the hypothalamus. Aft...Continue Reading
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