LONG-TERM BEHAVIORAL AND BIOCHEMICAL EFFECTS OF 6-HYDROXYDOPAMINE INJECTIONS IN RAT CAUDATE-PUTAMEN
LONG-TERM BEHAVIORAL AND BIOCHEMICAL EFFECTS OF 6-HYDROXYDOPAMINE INJECTIONS IN RAT CAUDATE-PUTAMEN
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DOI：
10.1016/0361-9230(91)90164-f
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发表时间：
1991-05-01
影响因子：
3.8
通讯作者：
JACKSONLEWIS, V
中科院分区：
文献类型：
--
作者：
CADET, JL;LAST, R;JACKSONLEWIS, V
单侧注射6-羟基多巴胺到大鼠纹状体导致安非他明诱导的盘旋行为。 这种旋转行为与几乎完全消失的desmethylimipramine不敏感的[H-3]马吲哚结合位点-这代表多巴胺摄取位点-在同侧尾壳核（CPu），黑质pars腹侧被盖区（SNPC），并在腹侧被盖区（VTA）。 在同侧CPu的特定分区中，[H-3]螺哌隆标记的多巴胺（DA）D2受体显著增加，背外侧（DL）和腹外侧（VL）区域显示DA D2受体显著增加。 同侧CPu的背内侧（DM）方面无显著增加，而该结构的腹内侧（VM）方面无变化。 相比之下，在6-OHDA诱导的病变同侧CPu的任何分区中，[H-3]SCH 23390标记的DA D1受体均无显着变化。 这些结果提供了证据表明，纹状体内注射6-OHDA导致大鼠脑中的生化变化，这与6-OHDA诱导的黑质病变后观察到的变化几乎相同。 纹状体内注射6-OHDA引起的这些长期生化效应进一步支持了以下观点：帕金森病患者脑中观察到的黑质DA细胞丢失可能继发于尾壳核内儿茶酚胺代谢过程中产生的氧自由基所致的逆行变化。
Unilateral injections of 6-hydroxydopamine into the rat striatum result in amphetamine-induced circling behavior. This rotational behavior was associated with an almost complete disappearance of desmethylimipramine-insensitive [H-3]mazindol binding sites-which represent dopamine uptake sites-in the ipsilateral caudate-putamen (CPu), the substantia nigra pars compacta (SNpc), and in the ventral tegmental area (VTA). There were significant increases in [H-3]spiperone-labeled dopamine (DA) D2 receptors in specific subdivisions of the ipsilateral CPu, with the dorsolateral (DL) and ventrolateral (VL) regions showing significant increases in DA D2 receptors. There were nonsignificant increases in the dorsomedial (DM) aspects of the ipsilateral CPu whereas there were no changes in the ventromedial (VM) aspects of that structure. In contrast, there were no significant changes in [H-3]SCH 23390-labeled DA D1 receptors in any of the subdivisions of the CPu ipsilateral to the 6-OHDA-induced lesions. These results provide evidence that intrastriatal injections of 6-OHDA result in biochemical changes in rat brain which are almost identical to those observed after 6-OHDA-induced lesions of the substantia nigra. These long-term biochemical effects caused by intrastriatal 6-OHDA injections provide further support for the idea that the nigral DA cell loss observed in the brains of parkinsonian patients could be secondary to retrograde changes due to oxyradicals generated during the metabolism of catecholamines within the caudate-putamen.