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      Central 5-HT 1A Receptors Inhibit Adrenocortical Secretion

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          Abstract

          Serotonin (5-HT) is generally considered to serve a facilitatory role in the regulation of adrenocortical secretion. Numerous studies have shown that administration of 5-HT1a receptor agonists increases plasma corticosterone (CS) concentrations in rats; however, the mechanism has not been established. Rats were prepared with a cannula implanted above the lateral cerebral ventricle, or bilateral cannulae above the hypothalamic paraventricular nuclei (PVN), the site of the perikarya of corticotropin-releasing factor (CRF)-secreting neurons regulating adrenocortical secretion. In sodium pen-tobarbital-anesthetized rats, intracerebroventricular and intra-PVN administration of 5-HT resulted in a multi-component dose-response curve in plasma CS, whereas administration of 5-HT in conscious animals resulted in low-dose inhibition and higher dose elevation of plasma CS levels. Under pentobarbital anesthesia, central administration of the selective 5-HT1a agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and ipsapirone decreased plasma CS levels, relative to saline-treated control rats, at all doses tested (0.001-20 nmol). In conscious rats, administration of 8-OH-DPAT decreased adrenocortical secretion at lower doses and significantly increased plasma CS concentrations at higher doses. Ipsapirone produced similar but less pronounced effects. In contrast, intraperitoneal injection of 8-OH-DPAT (2 µmol/kg) increased plasma CS concentrations, but this was not prevented by prior intracerebroventricular administration of the 5-HT1a antagonist, NAN-190 (5 nmol). Pentobarbital anesthesia completely blocked the plasma CS response to peripheral administration of 8-OH-DPAT. In view of the adrenocortical activating effects of hypotensive stimuli, we speculate that the well-documented hemodynamic changes following 5-HT1a receptor stimulation may be responsible for the adrenocortical responses observed. Our data demonstrate that low doses of 5-HT1a agonists delivered directly into the CNS decrease adrenocortical secretion. Since intra-PVN injections of 8-OH-DPAT to pentobarbital-anesthetized rats also decreased hypothalamo-pituitary-adrenocortical activity, it appears that a component of the inhibitory effect of 5-HT1a receptor activation is mediated by a direct effect at the level of the PVN, and presumably involves CRF-secreting neurons.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1993
          1993
          08 April 2008
          : 57
          : 2
          : 272-281
          Affiliations
          Departments of aPharmacology and Therapeutics, bPsychiatry, Louisiana State University Medical Center, Shreveport, La., USA
          Article
          126369 Neuroendocrinology 1993;57:272–281
          10.1159/000126369
          8510803
          © 1992 S. Karger AG, Basel

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          Page count
          Pages: 10
          Categories
          Original Paper

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