Suppression of serotogenic neuronal firing by α-adrenoceptor antagonists: Evidence against gaba mediation

Recent pharmacological studies have shown that the 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 the 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 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 interneurions 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 bicuculine methiodide, when appliee ionotophoretically 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-adrenoceptors. 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.