Moro Hiroomi, Sato Hirohito, Ida Itsurou, Oshima Akihiko, Sakurai Noriko, Shihara Nobuyuki, Horikawa Yukio, Mikuni Masahiko
Department of Psychiatry and Human Behavior, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Pharmacol Biochem Behav. 2007 May;87(1):56-64. doi: 10.1016/j.pbb.2007.03.020. Epub 2007 Apr 6.
Repeated administrations of psychostimulants into rodents produce behavioral sensitization. We examined whether a dopamine D1 agonist can reverse behavioral sensitization once established by repeated amphetamine (AMP) administrations and determined the mRNA expression levels of the D1 and D2 receptors, metabotropic glutamate receptor 1 (mGluR1), and activity-regulated cytoskeleton-associated protein (arc) in rats. Rats were pretreated with six intermittent AMP injections. Following a 14-day withdrawal period, the rats were divided into six groups and treated with either SKF-38393 (SKF; dopamine D1 agonist), SCH-23390 (SCH; selective D1 antagonist), YM-09151-2 (YM; selective D2 antagonist), SKF+SCH, SKF+YM or physiological saline once daily for 5 days. Three days or 4 weeks after the reversal treatments, all the rats were rechallenged with AMP. D1 and D2 antagonist treatments produced no significant decreases in locomotor activity or stereotyped behavior rate, respectively. In the SKF treatment group, stereotyped behavior rate decreased markedly after the three-day and four-week withdrawal periods. SKF+SCH treatment inhibited the effect of SKF treatment. The rats in the other groups that received AMP with or without SKF were decapitated 1 h after treatment, and the mRNA levels of the D1 and D2 receptors, mGluR1, and arc were measured by TaqMan real-time reverse transcriptase-polymerase chain reaction (RT-PCR). AMP administration significantly increased arc level. SKF also increased arc level significantly after the first single injection and after repeated injections of AMP during the pretreatment. There was no significant difference in arc expression level between the saline and SKF treatment groups after the AMP challenge, suggesting that arc expression level is not involved in the reversal effects of SKF in AMP sensitization.
对啮齿动物反复给予精神兴奋剂会产生行为敏化。我们研究了多巴胺D1激动剂是否能逆转由反复给予苯丙胺（AMP）所建立的行为敏化，并测定了大鼠中D1和D2受体、代谢型谷氨酸受体1（mGluR1）以及活性调节细胞骨架相关蛋白（arc）的mRNA表达水平。大鼠预先接受六次间歇性AMP注射。在14天的撤药期后，将大鼠分为六组，分别每日一次给予SKF-38393（SKF；多巴胺D1激动剂）、SCH-23390（SCH；选择性D1拮抗剂）、YM-09151-2（YM；选择性D2拮抗剂）、SKF+SCH、SKF+YM或生理盐水，持续5天。在逆转治疗后3天或4周，所有大鼠再次接受AMP激发。D1和D2拮抗剂治疗分别未使运动活性或刻板行为率显著降低。在SKF治疗组中，刻板行为率在三天和四周撤药期后显著降低。SKF+SCH治疗抑制了SKF治疗的效果。在接受AMP单独或联合SKF治疗的其他组大鼠于治疗后1小时断头，通过TaqMan实时逆转录聚合酶链反应（RT-PCR）测定D1和D2受体、mGluR1和arc的mRNA水平。给予AMP显著增加了arc水平。在首次单次注射后以及预处理期间反复注射AMP后，SKF也显著增加了arc水平。在AMP激发后，生理盐水组和SKF治疗组之间的arc表达水平无显著差异，这表明arc表达水平不参与SKF对AMP敏化的逆转作用。
