MESOLIMBIC DOPAMINE NEUROTRANSMISSION IS INCREASED BY ADMINISTRATION OF MU-OPIOID RECEPTOR ANTAGONISTS
MESOLIMBIC DOPAMINE NEUROTRANSMISSION IS INCREASED BY ADMINISTRATION OF MU-OPIOID RECEPTOR ANTAGONISTS
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DOI：
10.1016/0014-2999(93)90167-g
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发表时间：
1993-10-12
影响因子：
5
通讯作者：
WISE, RA
中科院分区：
文献类型：
--
作者：
DEVINE, DP;LEONE, P;WISE, RA
采用微透析和高压液相色谱法评估腹侧被盖区显微注射多阿片受体拮抗剂d - pens - tyr - d - trp - orn - thr - pens - thr - nh2 （CTOP）和β -富纳曲胺（β - fna）对细胞外腹侧纹状体多巴胺和代谢物浓度的影响。虽然已知CTOP可以拮抗细胞外腹侧纹状体多巴胺和多巴胺代谢物浓度的增加，这是由腹侧被盖区显微注射一种μ -阿片受体激动剂引起的，但当CTOP单独给药时，它会产生腹侧纹状体多巴胺和多巴胺代谢物浓度的剂量顺序增加。- fna也能提高多巴胺和代谢物浓度。这些类阿片受体拮抗剂的类阿片激动剂作用是出乎意料的，这表明在腹侧被盖区有一个复杂的局部电路介导阿片-多巴胺相互作用。由于已知mu-阿片类物质作用于含有γ -氨基丁酸（GABA）的腹侧被盖区神经元，因此提出了GABA能传入腹侧被盖区和腹侧被盖区GABA能中间神经元之间相互作用的模型。
Microdialysis and high pressure liquid chromatography were used to assess the effects of ventral tegmental area microinjections of the mu-opioid receptor antagoniStS D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and beta-funaltrexamine (beta-FNA) on extracellular ventral striatal dopamine and metabolite concentrations. While CTOP is known to antagonize the increases in extracellular ventral striatal dopamine and dopamine metabolite concentrations induced by ventral tegmental area microinjections of a mu-opioid receptor agonist, it produced dose-orderly increases in ventral striatal dopamine and dopamine metabolite concentrations when administered by itself. Beta-FNA also elevated dopamine and metabolite concentrations. These mu-agonist-like effects of the mu-opioid receptor antagonists were unexpected and suggest that a complex local circuitry mediates opioid-dopamine interactions in the ventral tegmental area. Since mu-opioids are known to act on ventral tegmental neurons that contain gamma-aminobutyric acid (GABA), a model of interactions between GABAergic afferents to the ventral tegmental area and ventral tegmental GABAergic interneurons is proposed.