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
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
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DOI：
10.1002/syn.22081
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发表时间：
2019-04-01
期刊：
影响因子：
2.3
通讯作者：
Saigusa, Tadashi
中科院分区：
文献类型：
--
作者：
Aono, Yuri;Watanabe, Yuriko;Saigusa, Tadashi
丘脑核中的胆碱能神经元含有被认为抑制神经活动的GABA（A）和GABA（B）受体。本研究采用在体微透析技术，分析了GABA（A）和GABA（B）受体在调节自由活动大鼠脑乙酰胆碱流出中的作用。由于多巴胺能神经元和胆碱能神经元可以相互作用，因此还分析了GABA受体配体对多巴胺流出的影响。通过透析探针向脑内施用药物。化合物的剂量表示在30-60分钟输注期间施用的总量（mol）。为了监测基础乙酰胆碱，将低浓度的毒扁豆碱（50 nM）加入灌注液中。GABA（A）受体激动剂蝇蕈醇（3和30 pmol）诱导剂量相关的乙酰胆碱减少。GABA（B）受体激动剂巴氯芬（30和300 pmol）也产生了剂量相关的乙酰胆碱减少。GABA（A）受体拮抗剂荷包牡丹碱（60 pmol）不能改变乙酰胆碱的基线，但能抵消蝇蕈醇（30 pmol）诱导的乙酰胆碱减少。GABA（B）受体拮抗剂2-羟基苯氯酚（12 nmol）不能改变乙酰胆碱的基线，但抵消了巴氯酚（300 pmol）诱导的乙酰胆碱减少。蝇蕈醇（30 pmol）和巴氯芬（300 pmol）都没有减少多巴胺的乙酰胆碱改变基线多巴胺。荷包牡丹碱（60 pmol）和2-羟基苯草胺（12 nmol）都不影响基线多巴胺。这些结果表明，GABA（A）和GABA（B）受体各自在脑胆碱能神经活动的调节中发挥抑制作用。目前的结果还提供了体内神经化学证据，即刺激GABA（A）和GABA（B）受体各自减少乙酰胆碱流出，而不影响自由活动大鼠延髓核中的多巴胺流出。
Cholinergic neurons in the nucleus accumbens contain GABA(A) and GABA(B) receptors that are thought to inhibit neural activity. We analyzed the roles of GABA(A) and GABA(B) 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. GABA(A) receptor agonist muscimol (3 and 30 pmol) induced a dose-related decrease in accumbal acetylcholine. GABA(B) receptor agonist baclofen (30 and 300 pmol) also produced a dose-related decrease in acetylcholine. GABA(A) receptor antagonist bicuculline (60 pmol) which failed to alter baseline acetylcholine counteracted the muscimol (30 pmol)-induced decrease in acetylcholine. GABA(B) 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 GABA(A) and GABA(B) 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 GABA(A) and GABA(B) receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.