The effects of corticotropin-releasing factor (CRF) and urocortins on the serotonin (hydroxytryptamine, 5HT) released from the raphe nuclei (RN)

Corticotropin-releasing factor (CRF) and urocortins (UCN1, UCN2 and UCN3) belong to the same CRF family of neuropeptides. They regulate the neuroendocrine, autonomic and behavioral responses to stress via two CRF receptors (CRF1 and CRF2). Stress, anxiety and depression affects the activity of the hypothalamic-pituitaryadrenal (HPA) axis and the serotoninergic neurotransmission, both being regulated by CRF and CRF-related peptides. However, the exact action of CRF and urocortins on the serotonin (5-hydroxytryptamine, 5HT) release was not fully elucidated yet. Therefore, the aim of the present study was to investigate the actions of CRF and urocortins on the 5HT released from the rat raphe nuclei (RN), the most important brain regions producing 5HT, and the participation of CRF receptors in these actions. In order to do so, male Wistar rats were used, their RN were isolated and dissected, and the RN slices were incubated with tritium-labelled 5HT, superfused and stimulated electrically. During superfusion, the RN slices were treated with CRF, UCN1, UCN2 or UCN3, and, when significant effect was observed, pretreated with selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin2B. The release of tritium-labelled 5HT from the RN was determined by liquid scintillation counting. CRF and UCN1 decreased significantly the tritium-labelled 5HT release from the RN, and these effects were reversed by antalarmin, but not by astressin2B. In addition, UCN3, but not UCN2, increased significantly the tritium-labelled 5HT release from the RN, and this effect was reduced by astressin2B, but not antalarmin. Our results indicate the existence of two apparently opposing CRF systems in the RN: activation of CRF1 by CRF and UCN1 may inhibit, whereas activation of CRF2 by UCN3 may stimulate the 5HT release. The dysbalance between CRF1 and CRF2 activation and, consequently, alteration of serotoninergic signalling may result in anxiety and depression, associated with hyperactivity of the HPA axis.