Reversion of muscarinic autoreceptor agonist‐induced acetylcholine decrease and learning impairment by dynorphin A (1–13), an endogenous κ‐opioid receptor agonist
Reversion of muscarinic autoreceptor agonist‐induced acetylcholine decrease and learning impairment by dynorphin A (1–13), an endogenous κ‐opioid receptor agonist
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强啡肽 A (1-13)（一种内源性 κ-阿片受体激动剂）可逆转毒蕈碱自身受体激动剂引起的乙酰胆碱减少和学习障碍
DOI：
10.1038/sj.bjp.0701671
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发表时间：
1998
影响因子：
7.3
通讯作者：
T. Kameyama
中科院分区：
文献类型：
--
作者：
M. Hiramatsu;H. Murasawa;H. Mori;T. Kameyama
1 我们研究了卡巴胆碱（一种毒蕈碱受体激动剂）是否会引起学习和记忆障碍，如果是的话，强啡肽 A (1-13)（一种内源性 κ-阿片受体激动剂）通过使用逐步式被动回避任务来改善卡巴胆碱引起的学习和记忆障碍。 2 卡巴胆碱诱导剂量相关的双重反应。将卡巴胆碱（每只大鼠 1.66 pmol）直接注射到海马可显着缩短步进潜伏期，而较低剂量（每只大鼠 0.166 pmol）和较高剂量（每只大鼠 16.6 pmol）卡巴胆碱不会引起学习或记忆障碍。 3 注射卡巴胆碱 5 分钟后给予强啡肽 A (1–13)（每只大鼠 0.5 纳摩尔，静脉注射）可显着逆转卡巴胆碱引起的学习和记忆障碍。 4 根据体内脑微透析测定，灌注卡巴胆碱 (3×10−4 M) 显着降低了灌注期间海马中乙酰胆碱的释放。低剂量阿托品（10−7 M）共灌注可抑制乙酰胆碱释放的减少。 5 强啡肽 A (1–13)（每只大鼠 0.5 nmol，静脉注射）在卡巴胆碱灌注前立即完全阻断卡巴胆碱引起的细胞外乙酰胆碱浓度下降。 6 强啡肽 A (1-13) 的这些拮抗作用可通过在强啡肽 A (1-13) 治疗前 5 分钟用去甲二醛托菲明（每只大鼠 5.44 nmol，静脉注射）（一种选择性 κ-阿片受体拮抗剂）治疗来消除。 7 这些结果表明，神经肽强啡肽 A (1-13) 可改善卡巴胆碱引起的学习和记忆障碍，同时减弱乙酰胆碱释放的减少，这可能与通过 κ-阿片受体导致突触前胆碱能神经元功能障碍有关。
1 We investigated whether carbachol, a muscarinic receptor agonist, induces learning and memory impairment, and if so, dynorphin A (1–13), an endogenous κ‐opioid receptor agonist, ameliorates the impairment of learning and memory induced by carbachol, by use of a step‐through type passive avoidance task. 2 Carbachol induced a dose‐related dual response. Carbachol (1.66 pmol per rat) administered directly into the hippocampus significantly shortened the step‐through latency, while lower (0.166 pmol per rat) and higher (16.6 pmol per rat) doses of carbachol did not induce learning or memory impairment. 3 Dynorphin A (1–13) (0.5 nmol per rat, i.c.v.) administered 5 min after carbachol injection significantly reversed carbachol‐induced impairment of learning and memory. 4 Perfusion with carbachol (3×10−4 M) significantly decreased acetylcholine release in the hippocampus during perfusion as determined by in vivo brain microdialysis. This decrease in acetylcholine release was suppressed by co‐perfusion with a low dose of atropine (10−7 M). 5 Dynorphin A (1–13) (0.5 nmol per rat, i.c.v.) immediately before carbachol perfusion completely blocked this decrease in extracellular acetylcholine concentration induced by carbachol. 6 These antagonistic effects of dynorphin A (1–13) were abolished by treatment with nor‐binaltorphimine (5.44 nmol per rat, i.c.v.), a selective κ‐opioid receptor antagonist, 5 min before dynorphin A (1–13) treatment. 7 These results suggest that the neuropeptide dynorphin A (1–13) ameliorates the carbachol‐induced impairment of learning and memory, accompanied by attenuation of the reductions in acetylcholine release which may be associated with dysfunction of presynaptic cholinergic neurones via κ‐opioid receptors.
影响因子：
56.9
作者：
MASH, DC;FLYNN, DD;POTTER, LT
通讯作者：
POTTER, LT
影响因子：
56.9
作者：
COYLE, JT;PRICE, DL;DELONG, MR
通讯作者：
DELONG, MR
阿片拮抗剂诱导的受体上调：同时施用激动剂的影响。
影响因子：
3.8
作者：
Yoburn,BC;Duttaroy,A;Shah,S;Davis,T
通讯作者：
Davis,T