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In vivo neurochemical evidence that stimulation of accumbal GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.
SYNAPSE ( IF 2.3 ) Pub Date : 2018-12-05 , DOI: 10.1002/syn.22081
Yuri Aono 1 , Yuriko Watanabe 2 , Manabu Ishikawa 3 , Noboru Kuboyama 1 , John L Waddington 4 , Tadashi Saigusa 1
Affiliation  

Cholinergic neurons in the nucleus accumbens contain GABAA and GABAB receptors that are thought to inhibit neural activity. We analyzed the roles of GABAA and GABAB receptors in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. The effects of GABA receptor ligands on the accumbal dopamine efflux were also analyzed because accumbal cholinergic and dopaminergic neurons could mutually interact. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 30-60 min infusions. To monitor basal acetylcholine, a low concentration of physostigmine (50 nM) was added to the perfusate. GABAA receptor agonist muscimol (3 and 30 pmol) induced a dose-related decrease in accumbal acetylcholine. GABAB receptor agonist baclofen (30 and 300 pmol) also produced a dose-related decrease in acetylcholine. GABAA receptor antagonist bicuculline (60 pmol) which failed to alter baseline acetylcholine counteracted the muscimol (30 pmol)-induced decrease in acetylcholine. GABAB receptor antagonist 2-hydroxysaclofen (12 nmol) which failed to change baseline acetylcholine, counteracted the baclofen (300 pmol)-induced decrease in acetylcholine. Neither muscimol (30 pmol) nor baclofen (300 pmol) which reduced accumbal acetylcholine altered baseline accumbal dopamine. Neither bicuculline (60 pmol) nor 2-hydroxysaclofen (12 nmol) also affected the baseline dopamine. These results show that GABAA and GABAB receptors each exert inhibitory roles in the regulation of accumbal cholinergic neural activity. The present results also provides in vivo neurochemical evidence that stimulation of GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.

中文翻译:

体内神经化学证据表明,刺激游离GABAA和GABAB受体均会降低乙酰胆碱外流,而不会影响自由移动大鼠伏隔核中的多巴胺外流。

伏伏核中的胆碱能神经元含有被认为抑制神经活动的GABAA和GABAB受体。我们分析了GABAA和GABAB受体在体内微透析中调节自由移动大鼠的累积乙酰胆碱流出的作用。还分析了GABA受体配体对伏安多巴胺流出的影响,因为伏安胆碱能神经元和多巴胺能神经元可以相互作用。通过透析探针在脑内施用药物。化合物剂量表示在输注30-60分钟期间的总给药量(摩尔)。为了监测基础乙酰胆碱,将低浓度的毒扁豆碱(50 nM)添加到灌注液中。GABAA受体激动剂麝香酚(3和30 pmol)引起了累积的乙酰胆碱剂量相关的降低。GABA B受体激动剂巴氯芬(30和300 pmol)也引起乙酰胆碱剂量相关的降低。未能改变基线乙酰胆碱的GABAA受体拮抗剂bicuculline(60 pmol)抵消了麝香酚(30 pmol)诱导的乙酰胆碱减少。无法改变基线乙酰胆碱的GABA B受体拮抗剂2-羟基沙氯芬(12 nmol)抵消了巴氯芬(300 pmol)诱导的乙酰胆碱下降。减少累积乙酰胆碱的muscimol(30 pmol)和巴氯芬(300 pmol)都不会改变基线累积多巴胺。双小分子(60 pmol)和2-羟基沙氯芬(12 nmol)均未影响基线多巴胺。这些结果表明,GABAA和GABAB受体在调节胆碱能神经活动中均起抑制作用。
更新日期:2019-11-01
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