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首页> 外文期刊>The European Journal of Neuroscience >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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Repeated administration of a dopamine D1 receptor agonist reverses the increased proportions of striatal dopamine D1High and D2High receptors in methamphetamine-sensitized rats.

机译：重复给予多巴胺D1受体激动剂可逆转甲基苯丙胺致敏大鼠中纹状体多巴胺D1High和D2High受体的比例增加。

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摘要

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.
机译：反复服用精神兴奋剂会引起行为过敏。苯丙胺敏感的动物在纹状体中具有较高比例的多巴胺D2受体（D2（高）受体）的高亲和力状态。我们最近报道，多巴胺D1受体激动剂R-（+）-SKF38393的重复给药会逆转已建立的对甲基苯丙胺（MAP）的行为敏感性。为了研究行为敏感性逆转的机制，我们研究了重复施用多巴胺D1受体激动剂对D2（高）受体的比例和多巴胺D1受体（D1（高）受体）的高亲和力状态的影响。纹状体。在MAP致敏大鼠的纹状体中，D1（高）和D2（高）受体的比例（28.5 +/- 1.96和57.5 +/- 3.58％）高于生理盐水对照组的大鼠（12.0 +分别为1.01和21.9 +/- 1.60％）。对MAP敏感的大鼠重复施用R-（+）-SKF38393可将D1（高）和D2（高）受体的增加比例分别降低至12.4 +/- 1.57和31.0 +/- 2.14％，这是相似的在盐水对照大鼠中的比例。在每种治疗条件下，多巴胺D1和D2受体的总密度没有改变。结果表明，在MAP致敏大鼠中纹状体中D1（High）和D2（High）受体的比例升高，向MAP致敏大鼠重复施用多巴胺D1受体激动剂可逆转D1的比例增加（高）和D2（高）受体。该发现揭示了通过重复施用多巴胺D1受体激动剂对MAP的行为敏化的发展和逆转已建立的敏化的突触后机制。

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