首页> 外文期刊>Addiction biology >The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for methamphetamine in rats with extended-access.
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The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for methamphetamine in rats with extended-access.

机译:多巴胺D3受体部分激动剂CJB090和拮抗剂PG01037降低了延长访问大鼠对甲基苯丙胺的反应进行性比率。

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Previous work suggests a role for dopamine D3-like receptors in psychostimulant reinforcement. The development of new compounds acting selectively at dopamine D3 receptors has opened new possibilities to explore the role of these receptors in animal models of psychostimulant dependence. Here we investigated whether the dopamine D3 partial agonist CJB090 (1-10 mg/kg, i.v) and the D3 antagonist PG01037 (8-32 mg/kg, s.c.) modified methamphetamine (0.05 mg/kg/injection) intravenous self-administration under fixed- (FR) and progressive- (PR) ratio schedules in rats allowed limited (short access, ShA; 1-hour sessions 3 days/week) or extended access (long access, LgA; 6 hour sessions 6 days/week). Under a FR1 schedule, the highest dose of the D3 partial agonist CJB090 selectively reduced methamphetamine self-administration in LgA but not in ShA rats, whereas the full D3 antagonist PG01037 produced no effect in either group. Under a PR schedule of reinforcement, the D3 partial agonist CJB090 reduced the maximum number of responses performed ('breakpoint') for methamphetamine in LgA rats at the doses of 5 and 10 mg/kg, and also it produced a significant reduction in the ShA group at the highest dose. However, the D3 full antagonist PG01037 only reduced PR methamphetamine self-administration in LgA rats at the highest dose of 32 mg/kg with no effect in the ShA group. The results suggest that rats might be more sensitive to pharmacological modulation of dopamine D3 receptors following extended access to methamphetamine self-administration, opening the possibility that D3 receptors play a role in excessive methamphetamine intake.
机译:先前的工作表明多巴胺D3样受体在精神刺激增强中的作用。选择性作用于多巴胺D3受体的新化合物的开发为探索这些受体在精神刺激依赖动物模型中的作用开辟了新的可能性。在这里我们研究了多巴胺D3部分激动剂CJB090(1-10 mg / kg,iv)和D3拮抗剂PG01037(8-32 mg / kg,sc)修饰的甲基苯丙胺(0.05 mg / kg /注射)静脉自用大鼠的固定(FR)和进行性(PR)比例表允许进行有限的访问(短期访问,ShA; 3小时/周的1小时训练)或扩展访问(长期访问,LgA; 6天/周的6小时训练)。在FR1方案下,最高剂量的D3部分激动剂CJB090在LgA中选择性降低了甲基苯丙胺的自我给药,但在ShA大鼠中则没有,而完全D3拮抗剂PG01037在两组中均未产生作用。在强化PR方案下,D3部分激动剂CJB090降低了剂量为5和10 mg / kg的LgA大鼠中对甲基苯丙胺的最大反应数量(“断点”),并且还显着降低了ShA最高剂量组。但是,D3完全拮抗剂PG01037仅在最高剂量32 mg / kg的LgA大鼠中减少了PR甲基苯丙胺的自我给药,而在ShA组中则没有作用。结果表明,大鼠在继续使用甲基苯丙胺自我给药后,可能对多巴胺D3受体的药理学调节更为敏感,这为D3受体在过量摄入甲基苯丙胺中发挥作用提供了可能性。

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