Inoue H
Radioisotope Institute for Basic and Clinical Medicine, Kurume University, School of Medicine, 67, Kurume, 830-0011, Asahi-machi, Japan.
Eur J Pharmacol. 2000 Oct 20;406(3):375-80. doi: 10.1016/s0014-2999(00)00703-2.
In order to characterize the effects of naltrexone, a mu-opioid receptor antagonist, on acute ethanol-induced functional modification of dopaminergic neurons in the nigrastriatal and mesolimbic dopamine systems, the accumulation of L-3, 4-dihydroxyphenylalanine (L-DOPA) in the cerebral cortex, dorsal striatum and nucleus accumbens and of 5-hydroxy-L-tryptophan (5-HTP) in the hippocampus was measured in normal rats using the mu-hydroxybenzylhydrazine dihydrochloride (NSD-1015) enzymatic inhibition method. In addition, the firing rates of dopaminergic neurons were recorded in the substantia nigra and ventral tegmental area. Naltrexone resulted in a decrease in the dopaminergic neuronal firing rates activated by ethanol and eventually in a reduction of the dopamine synthesis induced by ethanol in the dorsal striatum and nucleus accumbens, but not in the cerebral cortex. Mesolimbic dopamine neurons were slightly more sensitive to ethanol and naltrexone than were nigrostriatal dopamine neurons. The widespread inhibitory action of naltrexone also decreased the ethanol-induced stimulation of hippocampal serotonin synthesis.
为了表征μ-阿片受体拮抗剂纳曲酮对急性乙醇诱导的黑质纹状体和中脑边缘多巴胺系统中多巴胺能神经元功能改变的影响，采用盐酸μ-羟基苄基肼（NSD-1015）酶抑制法，在正常大鼠中测量了大脑皮质、背侧纹状体和伏隔核中L-3,4-二羟基苯丙氨酸（L-DOPA）以及海马体中5-羟基-L-色氨酸（5-HTP）的积累。此外，还记录了黑质和腹侧被盖区多巴胺能神经元的放电频率。纳曲酮导致乙醇激活的多巴胺能神经元放电频率降低，并最终导致乙醇诱导的背侧纹状体和伏隔核中多巴胺合成减少，但大脑皮质中未出现这种情况。中脑边缘多巴胺神经元比黑质纹状体多巴胺神经元对乙醇和纳曲酮的敏感性略高。纳曲酮广泛的抑制作用也降低了乙醇诱导的海马体5-羟色胺合成刺激。
