Kappa opioid receptor-mediated regulation of dopaminergic neurons in the rat brain.
Kappa opioid receptor-mediated regulation of dopaminergic neurons in the rat brain.
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发表时间：
1991-02
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通讯作者：
J. Manzanares;K. Lookingland;K. E. Moore
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作者：
J. Manzanares;K. Lookingland;K. E. Moore
在基础和刺激条件下，研究了κ阿片受体激动剂U-50，488 [反式-3，4-二氯-N-甲基-N-[2-吡咯烷基]-环己基]-苯乙酰胺]对雄性大鼠脑内包括黑质纹状体、中脑边缘、结节漏斗和结节垂体系统的多巴胺（DA）神经元活性的影响。DA神经元活性通过测量：1）给予脱羧酶抑制剂后3，4-二羟基苯丙氨酸的蓄积和2）DA代谢物3，4-二羟基苯乙酸在脑（纹状体、丘脑核和正中隆起）和含有这些神经元终末的垂体区域（中叶和神经叶）中的浓度来估计。在基础（非刺激）条件下，U-50，488产生了剂量和时间相关的结节垂体DA神经元的活动减少，但未能改变黑质纹状体，中脑边缘或结节漏斗DA神经元的活动。U-50，488抑制结节垂体DA神经元基础活动的能力被κ阿片受体拮抗剂nor-binaltorphimine阻断。氟哌啶醇增加黑质纹状体，中脑边缘和中叶结节垂体DA神经元的活动，而催乳素增加结节漏斗DA神经元的活动。U-50，488降低氟哌啶醇处理大鼠黑质纹状体、中脑边缘和结节垂体DA能神经元的活性，降低催乳素处理大鼠结节漏斗DA能神经元的活性。这些结果表明，κ阿片受体的激活抑制所有DA神经元系统在大脑中，但这种效果对黑质纹状体，mesolimbic和tuberoinfundibular DA神经元是明显的，只有在这些神经元被激活。
The effect of the kappa opioid receptor agonist U-50,488 [trans-3,4-dichloro-N-methyl-N-[2-pyrrolindinyl)-cyclohexyl]-benze ne- acetamide] was examined on the activity of dopamine (DA) neurons comprising the nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophysial systems in the male rat brain under basal and stimulated conditions. DA neuronal activity was estimated by measuring: 1) the accumulation of 3,4-dihydroxyphenylalanine after administration of a decarboxylase inhibitor and 2) the concentration of the DA metabolite 3,4-dihydroxyphenyla-cetic acid in brain (striatum, nucleus accumbens and median eminence) and pituitary regions (intermediate lobe and neural lobe) containing terminals of these neurons. Under basal (non-stimulated) conditions, U-50,488 produced a dose- and time-related decrease in the activity of tuberohypophysial DA neurons, but failed to alter the activity of nigrostriatal, mesolimbic or tuberoinfundibular DA neurons. The ability of U-50,488 to inhibit the basal activity of tuberohypophysial DA neurons was blocked by pretreatment with the kappa opioid antagonist nor-binaltorphimine. The activity of nigrostriatal, mesolimbic and intermediate lobe tuberohypophysial DA neurons was increased by haloperidol, whereas the activity of tuberoinfundibular DA neurons was increased by prolactin. U-50,488 decreased the activity of nigrostriatal, mesolimbic and tuberohypophysial DA neurons in haloperidol-treated rats, and decreased the activity of tuberoinfundibular DA neurons in prolactin-treated rats. These results indicate that activation of kappa opioid receptors inhibits all DA neuronal systems in the brain, but that this effect on nigrostriatal, mesolimbic and tuberoinfundibular DA neurons is evident only after these neurons have been activated.