SUPPRESSION OF FIRING ACTIVITY OF 5-HT NEURONS IN THE DORSAL RAPHE BY ALPHA-ADRENOCEPTOR ANTAGONISTS
SUPPRESSION OF FIRING ACTIVITY OF 5-HT NEURONS IN THE DORSAL RAPHE BY ALPHA-ADRENOCEPTOR ANTAGONISTS
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DOI：
10.1016/0028-3908(80)90187-2
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发表时间：
1980-01-01
影响因子：
4.7
通讯作者：
AGHAJANIAN, GK
中科院分区：
文献类型：
--
作者：
BARABAN, JM;AGHAJANIAN, GK
以往的药理学研究表明，中缝背核5-HT5-羟色胺细胞的放电活动依赖于紧张性活动的中枢肾上腺素能系统。多种α-肾上腺素能受体拮抗剂，WB 4101(41.+-.20微克/公斤；ED50+-。SD)、哌罗生(0.64.+-.0.20 mg/kg)，胸腺胺(0.42.+-)。0.31 mg/kg)和3.0 mg/kg苯氧苯甲胺全身给药可抑制大鼠的放电活动。这些α-肾上腺素能受体拮抗剂，以及酚妥拉明和二氢麦角隐亭，在离子导入时也减少了5-羟色胺细胞的放电。系统应用时药物的效力顺序为WB-4101.mchgt。胡椒恶烷.simeq.甲氨喋呤；苯氧苯甲胺。这一排名与他们在经典的外周突触后α-肾上腺素受体上的活动有很好的相关性。微离子透射法应用的肾上腺素能激动剂(去甲肾上腺素；苯肾上腺素；α-甲基去甲肾上腺素；异丙肾上腺素；沙丁胺醇)在竞争性α-肾上腺素受体阻断期间恢复5-羟色胺细胞放电的效力顺序表明，该受体应被归类为α-1-肾上腺素受体类别。以往的解剖学研究表明，中缝背侧接受一种肾上腺素能输入。位于中缝背侧的去甲肾上腺素终末显然介导了5-羟色胺细胞放电所依赖的一种强直的活跃的肾上腺素能影响。
Previous pharmacological studies suggested that the firing activity of 5-HT 5-hydroxytryptamine cells of the dorsal raphe nucleus is dependent on a tonically active, central adrenergic system. A wide variety of .alpha.-adrenoceptor antagonists, WB 4101 (41 .+-. 20 .mu.g/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 systemically to rats. 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 .mchgt. piperoxan .simeq. thymoxamine > phenoxybenzamine. This ranking correlates well with their activity at classical peripheral post-synaptic .alpha.-adrenoceptors. The order of potency of microiontophoretically applied adrenergic agonists (norepinephrine > phenylephrine > .alpha.-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. Norepinephrine terminals, present in the dorsal raphe, apparently mediate a tonically active adrenergic influence upon which the firing of 5-HT cells depends.