Antagonist-induced increase in 5-HT1A-receptor expression in adult rat hippocampus and cortex

Syed Y. Abbas, Maria I. Nogueira, Efrain C. Azmitia

Research output: Contribution to journalArticle

Abstract

Many receptor antagonists function as reverse agonists on the signaling transduction pathway, but little is known about the action of these drugs on the regulation of receptor expression. Serotonin 1A (5-HT1A) receptor expression in 5-HT and serum-free fetal hippocampal cultures is increased in the presence of a specific 5-HT1A-receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl)-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635). To study the plasticity of postsynaptic 5-HT1A receptors in the presence of antagonist in vivo, adult Sprague Dawley rats were injected i.p. either once or twice daily with a dose of WAY 100635 (3 mg/kg) over a period of 3 days. The 5-HT1A receptor expression was detected by immunocytochemistry and light microscopy, and the receptor immunoreactivity (IR) in hippocampus subregions was quantitatively assessed by using a comparative computer-assisted morphometric analysis. Following the daily injections of WAY 100635, a significant increase in 5-HT1A receptor labeling in hippocampal neurons was recorded. This marked increase in 5-HT1A receptor expression, which occurred within 4 h after a single injection of WAY 100635, is evident on the somata membrane and dendritic processes of hippocampal and cortex layer V neurons. By contrast, no increase in 5-HT1A receptor-IR was observed after multiple daily injections at a low dose (1 mg/kg) of WAY 100635. Our study shows that a single or multiple daily injections of WAY 100635 can result in an increase in 5-HT1A receptor-IR. This increase in labeling is consistent with an enhanced expression of the receptor protein. The action of this "inverse agonist" may have clinical importance in disorders such as depression, epilepsy, and Alzheimer's disease in which 5-HT1A receptor levels are deficient.

Original languageEnglish (US)
Pages (from-to)531-539
Number of pages9
JournalSynapse
Volume61
Issue number7
DOIs
StatePublished - Jul 2007

Fingerprint

Receptor, Serotonin, 5-HT1A
Hippocampus
Injections
Serotonin 5-HT1 Receptor Antagonists
Neurons
Drug and Narcotic Control
Carisoprodol
Sprague Dawley Rats
N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
Microscopy
Epilepsy
Serotonin
Alzheimer Disease
Immunohistochemistry
Depression
Light
Membranes

Keywords

  • Dentate gyrus
  • Inverse agonist
  • Morphometric
  • Serotonin
  • WAY 100635

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology
  • Advanced and Specialized Nursing

Cite this

Antagonist-induced increase in 5-HT1A-receptor expression in adult rat hippocampus and cortex. / Abbas, Syed Y.; Nogueira, Maria I.; Azmitia, Efrain C.

In: Synapse, Vol. 61, No. 7, 07.2007, p. 531-539.

Research output: Contribution to journalArticle

Abbas, Syed Y. ; Nogueira, Maria I. ; Azmitia, Efrain C. / Antagonist-induced increase in 5-HT1A-receptor expression in adult rat hippocampus and cortex. In: Synapse. 2007 ; Vol. 61, No. 7. pp. 531-539.
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