Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor

The serotonergic dorsal raphe nucleus (DRN) is innervated by corticotropin-releasing factor (CRF)-immunoreactive fibers and contains CRF receptor-binding sites, suggesting that endogenous CRF regulates this system. The present study examined the possibility that CRF in the DRN regulates the release of serotonin (5-HT) in forebrain terminal regions. Intracerebroventricular administration of CRF produced a bimodal effect on extracellular levels of 5-HT in the lateral septum. Doses of 0.3 and 1.0 mug decreased extracellular 5-HT levels, whereas both a higher (3.0 mug) and a lower (0.1 mug) dose had no effect. The reduction of extracellular 5-HT in the lateral septum by CRF (0.3 mug, i.C.v.) was blocked by pretreatment with the CRF receptor antagonist D-PheCRF(12-41) (3.0 mug, i.c.v.). Direct administration of CRF (30 ng) into the DRN reduced extracellular 5-HT levels in the lateral septum and the striatum. Furthermore, injection of D-PheCRF(12-41) (10 ng) into the DRN before ventricular administration of CRF (0.3 mug, i.c.v.) blocked the decrease in extracellular 5-HT in both the lateral septum and striatum. Taken together these data support the hypothesis that CRF may modulate 5-HT release in terminal regions via its effects at the level of the DRN. This modulation supports a potential interaction between CRF and 5-HT in stress-related psychiatric disorders in which both systems have been implicated.