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The serotonergic dorsal raphé 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 μg decreased extracellular 5-HT levels, whereas both a higher (3.0 μg) and a lower (0.1 μg) dose had no effect. The reduction of extracellular 5-HT in the lateral septum by CRF (0.3 μg, i.c.v.) was blocked by pretreatment with the CRF receptor antagonistd-PheCRF12–41 (3.0 μg, 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-PheCRF12–41 (10 ng) into the DRN before ventricular administration of CRF (0.3 μg, 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.

Regulation of Serotonin Release in the Lateral Septum and Striatum by Corticotropin-Releasing Factor