Suppression of firing activity of 5-HT neurons in the dorsal raphe by alpha-adrenoceptor antagonists

J. M. Baraban, G. K. Aghajanian

Research output: Contribution to journalArticlepeer-review

Abstract

Previous pharmacological studies have suggested that the firing activity of 5-HT cells of the dorsal raphe nucleus is dependent on a tonically active, central adrenergic system. In this study, a wide variety of alpha-adrenoceptor antagonists, WB-4101 (41 ± 20 μg/kg; ED50 ± SD), piperoxan (0.64 ± 0.20 mg/kg), thymoxamine (0.42 ± 0.31 mg/kg) and phenoxybenzamine (3.0 mg/kg) were found to suppress firing when administered sytemically. These alpha-adrenoceptor antagonists, as well as phentolamine and dihydroergocryptine, also reduced 5-HT cell firing when applied iontophoretically. The order of potency of the drugs when applied systemically was WB-4101 ≫ piperoxan ∼- thymoxamine > phenoxybenzamine. This ranking correlates well with their activity at classical peripheral postsynaptic α-adrenoceptors. In addition, the order of potency of microiontophoretically applied adrenergic agonists (norepinephrine > phenylephrine > α-methylnorepinephrine > isoproterenol > salbutamol) in restoring 5-HT cell firing during competitive alpha-adrenoceptor blockade suggests that this receptor should be classified in the alpha-1-adrenoceptor category. Previous anatomical studies have demonstrated that the dorsal raphe receives an adrenergic input. Taken together, these findings suggest that NE terminals, present in the dorsal raphe, mediate a tonically active adrenergic influence upon which the firing of 5-HT cells depends.

Original languageEnglish (US)
Pages (from-to)355-363
Number of pages9
JournalNeuropharmacology
Volume19
Issue number4
DOIs
StatePublished - Apr 1980
Externally publishedYes

Keywords

  • WB-4101
  • alpha-adrenoceptor
  • dorsal raphe nucleus
  • phentolamine
  • piperoxan
  • thymoxamine

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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