首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >No change in dopamine D1 receptor in vivo binding in rats after sub-chronic haloperidol treatment.
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No change in dopamine D1 receptor in vivo binding in rats after sub-chronic haloperidol treatment.

机译:亚慢性氟哌啶醇治疗后大鼠体内多巴胺D1受体的体内结合没有变化。

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摘要

A frequent side effect in the long-term treatment of schizophrenia with the dopamine D2 antagonist haloperidol (HAL) is the appearance of tardive dyskinesia or, in animals, of repetitive involuntary vacuous chewing movements (VCMs). In rats, chronic HAL-induced or D1 receptor-stimulated VCMs are suppressed by D1 antagonists, suggesting that this behavioral supersensitivity is mediated by D1 receptors. The goal of this study was to investigate in vivo the possible relationship between D1 receptor binding and D1-mediated behavioral supersensitivity, after subchronic HAL treatments. D1 agonist R-SKF 82957 and antagonist SCH 23390, both labeled with carbon-11, were used to assess in vivo D1 receptor binding. Rats were treated with HAL (1.5 mg/kg, i.p.) or vehicle for 21 days, followed by a 4 day washout period. No significant difference was found in the regional brain binding of either radioligand. D1 receptor-mediated behaviors including VCMs, grooming, and rearing were measured in control or HAL-treated rats. VCMs were significantly increased in HAL-treated rats, suggesting D1 receptor stimulation and possibly receptor supersensitivity. This study failed to link the purported D1 receptor-mediated behaviors with in vivo receptor binding measures of R-[11C]SKF 82957 or [11C]SCH 23390 in rat brain regions.
机译:用多巴胺D2拮抗剂氟哌啶醇(HAL)长期治疗精神分裂症的常见副作用是出现迟发性运动障碍,或在动物中出现反复的非自愿性空腹咀嚼运动(VCM)。在大鼠中,慢性HAL诱导或D1受体刺激的VCM被D1拮抗剂抑制,表明这种行为超敏性是由D1受体介导的。这项研究的目的是研究亚慢性HAL治疗后D1受体结合与D1介导的行为超敏反应之间的可能关系。都用碳11标记的D1激动剂R-SKF 82957和拮抗剂SCH 23390用于评估体内D1受体的结合。用HAL(1.5mg / kg,腹膜内)或运载体治疗大鼠21天,然后进行4天的清除期。在任一放射性配体的区域脑结合中未发现显着差异。在对照组或经HAL处理的大鼠中测量了D1受体介导的行为,包括VCM,修饰和饲养。在接受HAL治疗的大鼠中,VCM显着增加,提示D1受体刺激并可能是受体超敏性。这项研究未能将声称的D1受体介导的行为与R- [11C] SKF 82957或[11C] SCH 23390在大鼠脑区域的体内受体结合措施联系起来。

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