Biggio G, Casu M, Corda M G, Di Bello C, Gessa G L
Science. 1978 May 5;200(4341):552-4. doi: 10.1126/science.205949.
The intraventricular injection of methionine-enkephalin (50 to 100 micrograms) or [d-Ala2]-methionine-enkephalinamide (1.5 to 12 micrograms), a synthetic enkephalin analog resistant to enzyme degradation, caused a marked dose-dependent increase in dihydroxyphenylacetic acid and homovanillic acid concentrations in the rat striatum. The [d-Ala2] analog increased the accumulation of dopa in the striatum after aromatic amino acid decarboxylase inhibition, indicating that it increased dopamine synthesis. At the highest doses used both enkephalins failed to modify brain serotonin metabolism. The monolateral microinjection of the [d-Ala2]] analog (3 to 6 micrograms) into the caudate nucleus increased the concentration of dihydroxyphenylacetic acid in the injected side, whereas bilateral injection increased the concentration of this compound in both caudate nuclei and caused catalepsy. The stimulant effect of the [d-Ala2] analog on dopamine synthesis in the striatum persisted after destruction of striatal postsynaptic dopamine receptors with kainic acid. The biochemical and behavioral effects of enkephalins were prevented by naloxone, a specific narcotic antagonist. The results indicate that enkephalins stimulate dopamine synthesis by an action on opioid receptors localized on dopaminergic nerve terminals.
向大鼠脑室内注射甲硫氨酸脑啡肽（50至100微克）或[D - Ala2] - 甲硫氨酸脑啡肽酰胺（1.5至12微克，一种对酶降解有抗性的合成脑啡肽类似物），可使大鼠纹状体内的二羟基苯乙酸和高香草酸浓度出现明显的剂量依赖性增加。在抑制芳香族氨基酸脱羧酶后，[D - Ala2]类似物可增加纹状体内多巴的蓄积，表明其增加了多巴胺的合成。在使用的最高剂量下，两种脑啡肽均未能改变脑内5-羟色胺的代谢。向尾状核单侧微量注射[D - Ala2]类似物（3至6微克）可使注射侧的二羟基苯乙酸浓度升高，而双侧注射则可使双侧尾状核内该化合物的浓度升高并引起僵住症。在用 kainic 酸破坏纹状体突触后多巴胺受体后，[D - Ala2]类似物对纹状体多巴胺合成的刺激作用仍然存在。脑啡肽的生化和行为学效应可被特异性阿片拮抗剂纳洛酮阻断。结果表明，脑啡肽通过作用于多巴胺能神经末梢上的阿片受体来刺激多巴胺合成。
