TY - JOUR
T1 - Suppression of serotogenic neuronal firing by α-adrenoceptor antagonists
T2 - Evidence against gaba mediation
AU - Baraban, Jay M.
AU - Aghajanian, George K.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1980
Y1 - 1980
N2 - 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.
AB - 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.
KW - Dorsal raphe
KW - GABA antagonist
KW - Norepinephrine
KW - Serotonin neurons
KW - α-Adrenoceptor
UR - http://www.scopus.com/inward/record.url?scp=0018822821&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0018822821&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(80)90461-6
DO - 10.1016/0014-2999(80)90461-6
M3 - Article
C2 - 6106551
AN - SCOPUS:0018822821
SN - 0014-2999
VL - 66
SP - 287
EP - 294
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 4
ER -