Stimulation of accumbal GABAB receptors inhibits delta1- and delta2-opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats
Stimulation of accumbal GABAB receptors inhibits delta1- and delta2-opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats
复制标题
刺激伏隔 GABAB 受体抑制自由活动大鼠伏核中 delta1 和 delta2 阿片受体介导的多巴胺流出
DOI：
10.1016/j.ejphar.2018.08.003
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发表时间：
2018
影响因子：
5
通讯作者：
Tadashi Saigusa
中科院分区：
文献类型：
--
作者：
Yuriko Watanabe;Yuri Aono;Masamichi Komiya;John L Waddington;Tadashi Saigusa
延髓核含有δ-阿片受体，可以减少抑制性神经传递。由于GABA B受体抑制多巴胺释放，GABA B受体活化的减少可能是δ-阿片受体诱导的多巴胺外排的介导者。如果是这样的话，δ-阿片受体激活诱导的多巴胺外排应该通过刺激GABA受体来抑制。由于δ-阿片受体进一步细分为δ 1和δ 2-阿片受体，我们分析了GABA受体激动剂巴氯芬对δ 1和δ 2-阿片受体介导的自由活动大鼠体内多巴胺外排的影响。通过透析探针向脑内施用药物。化合物的剂量显示在25-50分钟输注期间施用的总量（mol）。巴氯芬（2.5和5.0 nmol），这并没有改变基础多巴胺水平，抑制δ 1-阿片受体激动剂DPDPE（5.0 nmol）诱导的多巴胺流出。巴氯芬（2.5和5.0 nmol）也抑制δ 2-阿片受体激动剂deltorphin II（25.0 nmol）诱导的多巴胺外排。低剂量的GABA受体拮抗剂2-羟基苯氯芬（100.0 pmol）不能改变基础多巴胺水平，但可抵消巴氯芬（5.0 nmol）对DPDPE（5.0 nmol）和deltorphin II（25.0 nmol）诱导的多巴胺外排的抑制作用。目前的结果表明，减少β-GABA受体介导的β-多巴胺能活性抑制促进δ 1-和δ 2-阿片受体诱导的β-多巴胺流出增加的激活。本研究表明，激活GABA能中间神经元胞体和/或终末上的δ 1-和δ 2-阿片受体抑制GABA释放，从而减少GABA受体介导的多巴胺能终末抑制，导致多巴胺流出增强。
The nucleus accumbens contains delta-opioid receptors that may decrease inhibitory neurotransmission. As GABABreceptors inhibit dopamine release, decrease in activation of GABABreceptors may be a mediator of delta-opioid receptor-induced accumbal dopamine efflux. If so, accumbal dopamine efflux induced by delta-opioid receptor activation should be suppressed by stimulating GABABreceptors. As delta-opioid receptors are further subdivided into delta1- and delta2-opioid receptors, we analysed the effects of the GABABreceptor agonist baclofen on delta1- and delta2-opioid receptor-mediated accumbal dopamine efflux in freely moving rats usingin vivomicrodialysis. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds show total amount administered (mol) during 25–50 min infusions. Baclofen (2.5 and 5.0 nmol), which did not alter basal dopamine levels, inhibited the delta1-opioid receptor agonist DPDPE (5.0 nmol)-induced dopamine efflux. Baclofen (2.5 and 5.0 nmol) also inhibited the delta2-opioid receptor agonist deltorphin II (25.0 nmol)-induced dopamine efflux. A low dose of the GABABreceptor antagonist 2-hydroxysaclofen (100.0 pmol), which failed to alter basal accumbal dopamine levels, counteracted the inhibitory effects of baclofen (5.0 nmol) on DPDPE (5.0 nmol)- and deltorphin II (25.0 nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABABreceptor-mediated inhibition of accumbal dopaminergic activity facilitates activation of delta1- and delta2-opioid receptor-induced increases in accumbal dopamine efflux. This study suggests that activation of delta1- and delta2-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABABreceptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux.