Role of D1-like receptors in amphetamine-induced behavioral sensitization:: a study using D1A receptor knockout mice
Role of D1-like receptors in amphetamine-induced behavioral sensitization:: a study using D1A receptor knockout mice
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DOI：
10.1007/s00213-001-0936-7
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发表时间：
2002-02-01
影响因子：
3.4
通讯作者：
Crawford, CA
中科院分区：
文献类型：
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作者：
Karper, PE;De la Rosa, H;Crawford, CA
理由：已使用 D-1 样受体拮抗剂 SCH 23390 和 D-1A 受体敲除小鼠（即 D-1A 缺陷型小鼠）检查了 D-1 样受体在安非他明诱导的行为敏化中所起的作用。使用这两种方法的研究提供了关于 D-1 样受体对于安非他明诱导的行为敏化的重要性的相互矛盾的证据。目的：本研究的目的是确定：(a) D-1A 缺陷小鼠在戒毒 3 天和 17 天后是否表现出苯丙胺诱导的运动敏化，以及 (b) SCH 23390 是否与 D-1A 和 D-1B 受体亚型结合。阻断野生型和 D-1A 缺陷小鼠中苯丙胺致敏的发展。方法：在第一个实验中，成年野生型和 D-1A 缺陷小鼠连续 7 天注射安非他明（0、1、2、4 或 8 mg/kg，IP）。在第二个实验中，野生型和 D-1A 缺陷型小鼠在注射安非他明（0 或 8 mg/kg，IP）前 30 分钟用 SCH 23390（0、0.15 或 0.5 mg/kg，IP）预处理。每天注射安非他明后。将小鼠置于活动室中，测量其行进距离（即水平运动活动）60 分钟。在戒毒 3 或 17 天后的测试日，给小鼠注射 1 mg/kg 安非他明，并测量 120 分钟的运动。结果：野生型和 D-1A 缺陷型小鼠均表现出安非他明诱导的运动敏化。用 0.5 mg/kg SCH 23390 预处理可阻断野生型小鼠运动敏化的发展，但不会改变 D-1A 缺陷型小鼠的敏化反应。结论：D-1 样受体似乎对于野生型小鼠苯丙胺敏化的发生是必需的，而 D-1A 和 D-1B 受体亚型对于苯丙胺诱导的 D-1A 缺陷小鼠的运动敏化都不是必需的。对这些相互矛盾的结果的一个可能解释是，D-1A 缺陷小鼠可能具有补偿机制（不涉及 D-1B 受体），使它们能够在缺乏 D-1A 受体的情况下表现出安非他明诱导的行为敏化。
Rationale: The role played by D-1-like receptors in amphetamine-induced behavioral sensitization has been examined using both the D-1-like receptor antagonist, SCH 23390, and the D-1A receptor knockout mouse (i.e. D-1A-deficient mice). Studies using these two approaches have provided conflicting evidence about the importance of D-1-like receptors for amphetamine-induced behavioral sensitization. Objective: The purpose of the present study was to determine: (a) whether D-1A-deficient mice exhibit amphetamine-induced locomotor sensitization after 3 and 17 drug abstinence days, and (b) whether SCH 23390, which binds to both D-1A and D-1B receptor subtypes. blocks development of amphetamine sensitization in wild-type and D-1A-deficient mice. Methods: In the first experiment, adult wild-type and D-1A-deficient mice were injected with amphetamine (0, 1, 2, 4, or 8 mg/kg, IP) for 7 consecutive days. In the second experiment, wild-type and D-1A-deficient mice were pretreated with SCH 23390 (0, 0.15, or 0.5 mg/kg, IP) 30 min prior to being injected with amphetamine (0 or 8 mg/kg. IP). After each daily amphetamine injection. mice were placed in activity chambers where distance traveled (i.e. horizontal locomotor activity) was measured for 60 min. On the test days, which occurred after 3 or 17 drug abstinence days, mice were injected with I mg/kg amphetamine and locomotion was measured for 120 min. Results: Both wild-type and D-1A-deficient mice exhibited amphetamine-induced locomotor sensitization. Pretreatment with 0.5 mg/kg SCH 23390 blocked the development of locomotor sensitization in wild-type mice, but did not alter the sensitized responding of D-1A-deficient mice. Conclusions: It appears that D-1-like receptors are necessary for the development of amphetamine sensitization in wild-type mice, while neither the D-1A nor D-1B receptor subtypes are necessary for the amphetamine-induced locomotor sensitization of D-1A-deficient mice. A possible explanation for these conflicting results is that D-1A-deficient mice may have a compensatory mechanism (not involving, D-1B receptors) that allows them to exhibit amphetamine-induced behavioral sensitization in the absence of the D-1A receptor.