OPPOSING TONICALLY ACTIVE ENDOGENOUS OPIOID SYSTEMS MODULATE THE MESOLIMBIC DOPAMINERGIC PATHWAY
OPPOSING TONICALLY ACTIVE ENDOGENOUS OPIOID SYSTEMS MODULATE THE MESOLIMBIC DOPAMINERGIC PATHWAY
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DOI：
10.1073/pnas.89.6.2046
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发表时间：
1992-03-15
影响因子：
11.1
通讯作者：
SHIPPENBERG, TS
中科院分区：
文献类型：
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作者：
SPANAGEL, R;HERZ, A;SHIPPENBERG, TS
中脑边缘多巴胺能系统与阿片类药物和其他滥用药物的动机效应有关。阿片样物质在该系统中的作用位置以及内源性阿片样肽在其中调节多巴胺活性的作用尚不清楚。本研究采用体内微透析技术和高选择性阿片配体的管理，证明了在A10多巴胺能神经元的主要终末区伏隔核中存在张力活性和功能对立的mu和kappa-阿片系统，它们调节多巴胺释放。因此，刺激腹侧被盖区（A10多巴胺能神经元的起源部位）的mu型受体增加多巴胺释放，而选择性阻断这种阿片受体类型导致基底多巴胺释放显著减少。相比之下，刺激伏隔核内的kappa型受体会减少多巴胺的释放，而它们的选择性阻断会显著增加基底多巴胺的释放。这些数据表明，mu和kappa受体的强直性激活是维持伏隔核基底多巴胺释放所必需的。鉴于中边缘系统在药物诱导的情绪和情感改变的调解中的假设作用，这些发现可能对阿片类药物依赖和情感障碍的治疗有影响。
The mesolimbic dopaminergic system has been implicated in mediating the motivational effects of opioids and other drugs of abuse. The site of action of opioids within this system and the role of endogenous opioid peptides in modulating dopamine activity therein remain unknown. Employing the technique of in vivo microdialysis and the administration of highly selective opioid ligands, the present study demonstrates the existence of tonically active and functionally opposing-mu and kappa-opioid systems that regulate dopamine release in the nucleus accumbens, the major terminal area of A10 dopaminergic neurons. Thus, stimulation of mu-type receptors in the ventral tegmental area, the site of origin of A10 dopaminergic neurons, increases dopamine release whereas the selective blockade of this opioid receptor type results in a significant decrease in basal dopamine release. In contrast, stimulation of kappa-type receptors within the nucleus accumbens decreases dopamine release whereas their selective blockade markedly increases basal dopamine release. These data show that tonic activation of mu and kappa-receptors is required for the maintenance of basal dopamine release in the nucleus accumbens. In view of the postulated role of the mesolimbic system in the mediation of drug-induced alterations in mood and affect, such findings may have implications for the treatment of opiate dependence and affective disorders.