Repeated administration of a dopamine D1 receptor agonist reverses the increased proportions of striatal dopamine D1High and D2High receptors in methamphetamine-sensitized rats
Repeated administration of a dopamine D1 receptor agonist reverses the increased proportions of striatal dopamine D1High and D2High receptors in methamphetamine-sensitized rats
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DOI：
10.1111/j.1460-9568.2008.06221.x
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发表时间：
2008-05-01
影响因子：
3.4
通讯作者：
Nishi, Akinori
中科院分区：
文献类型：
--
作者：
Shuto, Takahide;Seeman, Philip;Nishi, Akinori
反复服用精神刺激剂会产生行为敏感化。已知苯丙胺致敏的动物在纹状体中有较高比例的多巴胺D2受体(D2(High)受体)的高亲和力状态。我们最近报道，反复给予多巴胺D1受体激动剂R-(+)-SKF38393，可以逆转对甲基苯丙胺(MAP)的行为敏化。为了探讨行为敏化逆转的机制，我们观察了重复给予多巴胺D_1受体激动剂对纹状体D_2(高)受体比例和D_1受体(D_1(高)受体)高亲和力的影响。MAP致敏大鼠纹状体内D1(High)和D2(High)受体的比例(28.5+/-1.96和57.5+/-3.58%)高于生理盐水对照组(分别为12.0+/-1.01和21.9+/-1.60%)。反复给予R-(+)-SKF38393可使MAP致敏大鼠脑内D_1(High)和D_2(High)受体比例分别升高至12.4+/-1.57%和31.0+/-2.14%，与生理盐水对照组相似。多巴胺D_1和D_2受体的总密度在各处理条件下均无改变。结果表明，MAP致敏大鼠纹状体内D_1(High)和D_2(High)受体比例升高，反复给予多巴胺D_1受体激动剂可逆转D_1(High)和D_2(High)受体比例的增加。这些发现揭示了突触后发展对MAP的行为敏化的机制，以及通过重复给予多巴胺D1受体激动剂逆转已建立的敏化。
Repeated administration of psychostimulants produces a behavioural sensitization. Amphetamine-sensitized animals are known to have a higher proportion of high-affinity states of dopamine D2 receptors (D2(High) receptors) in the striatum. We recently reported that repeated administration of a dopamine D1 receptor agonist, R-(+)-SKF38393, reverses the established behavioural sensitization to methamphetamine (MAP). To investigate the mechanisms for reversal of behavioural sensitization, we examined the effect of repeated administration of the dopamine D1 receptor agonist on the proportions of D2(High) receptors and the high-affinity states of dopamine D1 receptors (D1(High) receptors) in the striatum. In the striatum from the MAP-sensitized rats, the proportions of D1(High) and D2(High) receptors (28.5 +/- 1.96 and 57.5 +/- 3.58%) were higher than those in the saline-control rats (12.0 +/- 1.01 and 21.9 +/- 1.60%, respectively). Repeated administration of R-(+)-SKF38393 to the MAP-sensitized rats reduced the increased proportions of D1(High) and D2(High) receptors to 12.4 +/- 1.57 and 31.0 +/- 2.14%, respectively, which were similar to the proportions in the saline-control rats. The total densities of dopamine D1 and D2 receptors were not altered in each treatment condition. The results demonstrate that the proportions of D1(High) and D2(High) receptors in the striatum are elevated in MAP-sensitized rats, and that repeated administration of the dopamine D1 receptor agonist to the MAP-sensitized rats reverses the increased proportions of D1(High) and D2(High) receptors. The findings reveal postsynaptic mechanisms for the development of behavioural sensitization to MAP and the reversal of established sensitization by repeated administration of the dopamine D1 receptor agonist.