Trovero F, Herve D, Desban M, Glowinski J, Tassin J P
Laboratoire de Neuropharmacologie, INSERM U.114, Collège de France, Paris.
Neuroscience. 1990;39(2):313-21. doi: 10.1016/0306-4522(90)90270-e.
In rat striatal slices, the autoradiographic analysis of [3H]naloxone binding allows one to define highly labelled patches corresponding to the striosomes and representing about 17% of the total striatal volume, surrounded by a poorly labelled zone, the matrix. Previous studies have shown that the density of these mu-opiate receptor binding sites is decreased by about 28% following destruction of the striatal dopamine innervation suggesting a partial localization of these receptors on dopamine presynaptic nerve endings. These results were confirmed but, in addition, we have shown that a chronic (30 days) blockade of dopamine transmission obtained by treatment of the animals with a long acting neuroleptic induces a similar decrease of mu binding sites. Further experiments made with D-Pen2,D-Pen5-[tyrosyl-3-5(n)-3H] enkephalin, a selective delta opiate receptor agonist, have revealed that the density of delta opiate binding sites is decreased (30%) in rats with striatal dopamine denervation but not in those treated with the long acting neuroleptic. These data indicate that part of these delta receptors is located on dopamine nerve terminals but are not in favour of the presence of mu receptors on these nerve terminals. The decrease in [3H]naloxone binding sites induced by prolonged interruption of dopamine transmission can be attributed to postsynaptic events.
在大鼠纹状体切片中,通过对[3H]纳洛酮结合进行放射自显影分析,能够确定对应于纹状体小体的高度标记斑块,这些斑块约占纹状体总体积的17%,其周围是标记较弱的区域,即基质。先前的研究表明,在破坏纹状体多巴胺神经支配后,这些μ阿片受体结合位点的密度降低了约28%,这表明这些受体部分定位于多巴胺突触前神经末梢。这些结果得到了证实,但此外,我们还表明,用长效抗精神病药物治疗动物导致的多巴胺传递慢性(30天)阻断会引起类似的μ结合位点减少。用选择性δ阿片受体激动剂D-青霉胺2,D-青霉胺5-[酪氨酰-3-5(n)-3H]脑啡肽进行的进一步实验表明,纹状体多巴胺去神经支配的大鼠中δ阿片结合位点的密度降低(30%),但用长效抗精神病药物治疗的大鼠中则未降低。这些数据表明,这些δ受体部分位于多巴胺神经末梢,但不支持这些神经末梢上存在μ受体。多巴胺传递长期中断所诱导的[3H]纳洛酮结合位点减少可归因于突触后事件。