Suppression of serotonergic neuronal firing by α-adrenoceptor antagonists: Evidence against GABA mediation

Jay M Baraban, G. K. Aghajanian

Research output: Contribution to journalArticle

Abstract

Recent pharmacological studies have shown that administration of α-adrenoceptor antagonists, either systemically or locally in the vicinity of 5-HT cells of the dorsal raphe, suppresses their firing activity. In light of the prominent NE innervation of the dorsal raphe nucleus, these findings suggest that blockade of NE transmission in the dorsal raphe by these drugs underlies the suppression produced. The finding that systemic administration of picrotoxin, a GABA antagonist, partially reverses the suppression of 5-HT cells produced by systemic application of α-adrenoceptor antagonists led to the proposal that GABA interneurons located within the dorsal raphe mediate this suppression of 5-HT cell firing. This proposal has been tested, in this study, by examining the ability of two GABA antagonists, picrotoxin and bicuculline methiodide, when applied iontophoretically to reverse the suppression produced by two α-adrenoceptor antagonists, WB-4101 and phentolamine. First, evidence is presented that WB-4101 and phentolamine suppress 5-HT cell firing specifically by their blockade of α-adrenoreceptors. Second, the inability of both GABA antagonists tested to interfere with the suppression produced by these α-adrenoceptor antagonists is reported. These findings provide evidence against the proposal that GABA mediates the suppression of 5-HT cells by α-adrenoceptor antagonists.

Original languageEnglish (US)
Pages (from-to)287-294
Number of pages8
JournalEuropean Journal of Pharmacology
Volume66
Issue number4
StatePublished - 1980
Externally publishedYes

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gamma-Aminobutyric Acid
Adrenergic Receptors
Serotonin
GABA Antagonists
Picrotoxin
Phentolamine
Interneurons
Pharmacology
Dorsal Raphe Nucleus
Pharmaceutical Preparations
(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Suppression of serotonergic neuronal firing by α-adrenoceptor antagonists : Evidence against GABA mediation. / Baraban, Jay M; Aghajanian, G. K.

In: European Journal of Pharmacology, Vol. 66, No. 4, 1980, p. 287-294.

Research output: Contribution to journalArticle

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