Suppression of serotonergic neuronal firing by alpha-adrenoceptor antagonists: evidence against GABA mediation.

Recent pharmacological studies have shown that administration of alpha-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 alpha-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 alpha-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 alpha-adrenoreceptors. Second, the inability of both GABA antagonists tested to interfere with the suppression produced by these alpha-adrenoceptor antagonists is reported. These findings provide evidence against the proposal that GABA mediates the suppression of 5-HT cells by alpha-adrenoceptor antagonists.