5-HT1A RECEPTOR AGONIST FLESINOXAN ENHANCES FOS IMMUNOREACTIVITY IN RAT CENTRAL AMYGDALA, BED NUCLEUS OF THE STRIA TERMINALIS AND HYPOTHALAMUS

5-Hydroxytryptamine-1A (5-HT1A) receptor agonists, including flesinoxa n, 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 e arly gene protein product Fos (Fos-ir) in rat brains 1 h after flesino xan 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 no t show Fos-ir. Apparently, binding of flesinoxan at the 5-HT1A recepto r does not directly lead to activation of c-fos in the cell, probably due to its negative coupling to adenylate cyclase. However, in typical ly non-5HT(1A) receptor-containing brain areas Fos-ir is increased due to flesinoxan treatment, as in the paraventricular nucleus of the hyp othalamus (PVN), the dorsolateral part of the bed nucleus of the stria terminalis (BNSTdl) and the central amygdala (CeA). Flesinoxan-treate d rats also exhibited higher plasma corticosterone levels than vehicle -treated animals, which suggests the involvement of corticotropin-rele asing hormone (CRH) or vasopressin in the hypothalamus. After double i mmunolabelling (Fos/CRH or Fos/vasopressin), every CRH neuron detected in the PVN also contained Fos. Moreover, a significant correlation ex isted between the number of Fos-ir neurons in the PVN and the plasma c orticosterone level. Hardly any Fos/vasopressin double labelling was v isible in the PVN. Accordingly, flesinoxan exerts its activating effec ts on the HPA axis via CRH neurons in the PVN. These effects are trans -synaptically mediated by other brain areas, such as the CeA and BNSTd l, which also show increased Fos-ir.