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Original Article |
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Neuropsychopharmacology (2000) 22 148-162.10.1038/sj.npp.1395417
Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus
Lynn G Kirby1 Ph.D, Kenner C Rice2 Ph.D and Rita J Valentino1 Ph.D |
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1Department of Psychiatry, Division of Stress Neurobiology, Medical College of Pennsylvania and Hahnemann University, Philadelphia, PA USA
2Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Mental Health, Bethesda, MD USA
Correspondence: Dr Lynn G Kirby, Department of Psychiatry; MS 403, Hahnemann University, Broad and Vine Streets, Philadelphia, PA 19102
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ABSTRACT
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The present study examined the regional localization of corticotropin-releasing factor (CRF)- and 5-hydroxytryptamine (5-HT)-immunoreactive (IR) fibers within the rat dorsal raphe nucleus (DRN) using immunohistochemistry. Additionally, the effects of CRF, administered intracerebroventricularly (0.1-3.0  g) or intraraphe (0.3-30 ng), on discharge rates of putative 5-HT DRN neurons were quantified using in vivo single unit recording in halothane-anesthetized rats. CRF-IR fibers were present at all rostrocaudal levels of the DRN and exhibited a topographical distribution. CRF produced predominantly inhibitory effects on DRN discharge at lower doses and these effects diminished or became excitatory at higher doses. Inhibition of DRN discharge by CRF was attenuated by the nonselective CRF antagonist, DPheCRF12-41 and the CRF-R1-selective antagonist, antalarmin, implicating the CRF-R1 receptor subtype in these electrophysiological effects. The present findings provide anatomical and physiological evidence for an impact of CRF on the DRN-5HT system.
Keywords: Corticotropin-releasing hormone; 5-hydroxytryptamine; Stress; Immunohistochemistry; Antalarmin; DPheCRF12-41 |
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