Desensitization of 5-HT1A receptors by 5-HT2A receptors in neuroendocrine neurons in vivo

Yahong Zhang, Thackery S. Gray, Deborah N. D'Souza, Gonzalo A. Carrasco, Katerina J. Damjanoska, Bertalan Dudas, Francisca Garcia, Gina M. Zainelli, Nicole R. Sullivan Hanley, George Battaglia, Nancy A. Muma, Louis D. Van De Kar

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

An imbalance between serotonin-2A (5-HT2A) and 5-HT1A receptors may underlie several mood disorders. The present studies determined whether 5-HT2A receptors interact with 5-HT1A receptors in the rat hypothalamic paraventricular nucleus (PVN). The sensitivity of the hypothalamic 5-HT1A receptors was measured as oxytocin and adrenocorticotropic hormone (ACTH) responses to the 5-HT1A receptor agonist (+)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide [(+)8-OH-DPA] (40 μg/kg s.c.). The 5-HT2A/2C receptor agonist (-)DOI [(-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCI] (1 mg/kg s.c.) injected 2 h prior to (+)8-OH-DPAT significantly reduced the oxytocin and ACTH responses to (+)8-OH-DPAT, producing a heterologous desensitization of the 5-HT 1A receptors. Microinjection of the 5-HT2A receptor antagonist MDL100,907 [(+)-α-(2,3dimethoxyphenyl)-1-[2-(4- fluorophenylethyl)]-4-piperidinemethanol; 0, 10, or 20 nmol, 15 min prior to (-)DOI] into the PVN dose-dependently prevented the desensitization of 5-HT 1A receptors induced by the 5-HT2A receptor agonist (-)DOI. Double-label immunocytochemistry revealed a high degree of colocalization of 5-HT1A and 5-HT2A receptors in the oxytocin and corticotropin-releasing factor neurons of the PVN. Thus, activation of 5-HT2A receptors in the PVN may directly induce a heterologous desensitization of 5-HT1A receptors within individual neuroendocrine cells. These findings may provide insight into the long-term adaptation of 5-HT1A receptor signaling after changes in function of 5-HT 2A receptors; for example, during pharmacotherapy of mood disorders.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume310
Issue number1
DOIs
StatePublished - Jul 2004

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Desensitization of 5-HT<sub>1A</sub> receptors by 5-HT<sub>2A</sub> receptors in neuroendocrine neurons in vivo'. Together they form a unique fingerprint.

Cite this