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毒蕈碱和α(1)-肾上腺素能机制参与大鼠中脑脚桥被盖核刺激诱导的抗伤害感受的脊髓介导。

Muscarinic and alpha(1)-adrenergic mechanisms contribute to the spinal mediation of stimulation-induced antinociception from the pedunculopontine tegmental nucleus in the rat.

作者信息

Dias Quintino M, Crespilho Simone F, Silveira João Walter S, Prado Wiliam A

机构信息

Department of Pharmacology, Faculty of Medicine of Ribeirão Preto-USP, Ribeirão Preto, SP, Brazil.

出版信息

Pharmacol Biochem Behav. 2009 May;92(3):488-94. doi: 10.1016/j.pbb.2009.01.018. Epub 2009 Jan 31.

DOI:10.1016/j.pbb.2009.01.018
PMID:19463264
Abstract

The effects of intraperitoneal (i.p.) or intrathecal (i.t.) injection of antagonists of acetylcholine, noradrenaline, serotonin, dopamine, opioids and GABA on stimulation-produced antinociception (SPA) from the pedunculopontine tegmental nucleus (PPTg) of rats were studied using the tail-flick test. The electrical stimulation of the PPTg produced a strong and long-lasting increase in tail-flick latency. The intensity and duration of the effect were significantly reduced in rats pretreated with i.p. or i.t. atropine (a non-selective muscarinic cholinergic antagonist), or i.t. phenoxybenzamine or WB 4101 (non-selective and selective alpha(1)-adrenergic antagonists, respectively). Intraperitoneal phenoxybenzamine, i.p. or i.t. methysergide or naloxone (non-selective serotonin and opioid antagonists, respectively), or i.t. idazoxan (a selective alpha(2)-adrenergic antagonist) only reduced the duration of the effect. The duration of SPA from the PPTg was increased by i.t. phaclofen (a GABA(B) antagonist). The effect from the nucleus was not altered following i.t. bicuculline (a GABA(A) antagonist), or i.p. or i.t. mecamylamine, propranolol or haloperidol (non-selective nicotinic cholinergic, beta-adrenergic and dopaminergic antagonists, respectively). Thus, SPA from the PPTg involves the spinal activation of muscarinic and alpha(1)-adrenergic but not nicotinic cholinergic, beta-adrenergic and dopaminergic mechanisms. Serotonergic, endogenous opioid and alpha(2)-adrenergic mechanisms are involved in the duration but not in the intensity of the effect.

摘要

采用甩尾试验,研究了腹腔注射(i.p.)或鞘内注射(i.t.)乙酰胆碱、去甲肾上腺素、5-羟色胺、多巴胺、阿片类物质和γ-氨基丁酸拮抗剂对大鼠脚桥被盖核(PPTg)刺激产生的抗伤害感受(SPA)的影响。对PPTg进行电刺激可使甩尾潜伏期显著延长且持续时间长。预先腹腔注射或鞘内注射阿托品(一种非选择性毒蕈碱胆碱能拮抗剂)、鞘内注射酚苄明或WB 4101(分别为非选择性和选择性α(1)-肾上腺素能拮抗剂)的大鼠,这种效应的强度和持续时间均显著降低。腹腔注射酚苄明、腹腔注射或鞘内注射甲基麦角新碱或纳洛酮(分别为非选择性5-羟色胺和阿片类拮抗剂)、或鞘内注射咪唑克生(一种选择性α(2)-肾上腺素能拮抗剂)仅能缩短效应持续时间。鞘内注射巴氯芬(一种GABA(B)拮抗剂)可延长PPTg产生的SPA持续时间。鞘内注射荷包牡丹碱(一种GABA(A)拮抗剂)、或腹腔注射或鞘内注射美加明、普萘洛尔或氟哌啶醇(分别为非选择性烟碱胆碱能、β-肾上腺素能和多巴胺能拮抗剂)后,该核团产生的效应未改变。因此,PPTg产生的SPA涉及毒蕈碱和α(1)-肾上腺素能的脊髓激活机制,而不涉及烟碱胆碱能、β-肾上腺素能和多巴胺能机制。5-羟色胺能、内源性阿片类和α(2)-肾上腺素能机制参与效应的持续时间,但不参与效应的强度。

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