Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor.
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 microg decreased extracellular 5-HT levels, whereas both a higher (3.0 microg) and a lower (0.1 microg) dose had no effect. The reduction of extracellular 5-HT in the lateral septum by CRF (0.3 microg, i.c.v.) was blocked by pretreatment with the CRF receptor antagonist d-PheCRF(12-41) (3.0 microg, 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 microg, 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.
Price
M L
ML
David Mahoney Institute of Neurological Sciences and Departments of Psychiatry and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Lucki
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D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D020665:Septum of Brain / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; C113202:phenylalanyl corticotropin-releasing factor (12-41); D012701:Serotonin; D003346:Corticotropin-Releasing Hormone