Yoshida H, Ohno M, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Brain Res Bull. 1995;38(4):393-7. doi: 10.1016/0361-9230(95)02005-c.
To elucidate the roles of dopamine D1 and D2 receptors in mediating strial Fos protein induction and behavioral sensitization after methamphetamine administration, we examined the effects of the D1 receptor antagonist SCH 23390 and D2 receptor antagonist sulpiride on these phenomena in rats. Intraperitoneal administration of 5.0 mg/kg methamphetamine produced a significant increase in Fos-immunoreactive cells in the medial striatum. Prior exposure to 5.0 mg/kg methamphetamine enhanced ipsilateral rotational behavior in response to subsequent methamphetamine administration in unilateral nigral-lesioned rats (sensitization). Pretreatment with SCH 23390 (0.32 mg/kg IP) suppressed significantly the expression of striatal Fos protein and the development of acute behavioral sensitization following a single injection of 5.0 mg/kg methamphetamine. Sulpiride (50 mg/kg IP) was also effective in suppressing methamphetamine behavioral sensitization, but did not affect the striatal Fos induction. These results suggest that dopamine D1 receptor-mediated mechanisms are involved in the striatal Fos protein induction associated with behavioral sensitization following exposure to methamphetamine.
为阐明多巴胺D1和D2受体在介导甲基苯丙胺给药后纹状体Fos蛋白诱导及行为敏化中的作用，我们研究了D1受体拮抗剂SCH 23390和D2受体拮抗剂舒必利对大鼠这些现象的影响。腹腔注射5.0 mg/kg甲基苯丙胺可使内侧纹状体中Fos免疫反应性细胞显著增加。预先给予5.0 mg/kg甲基苯丙胺可增强单侧黑质损伤大鼠对后续甲基苯丙胺给药的同侧旋转行为（敏化）。用SCH 23390（0.32 mg/kg腹腔注射）预处理可显著抑制单次注射5.0 mg/kg甲基苯丙胺后纹状体Fos蛋白的表达及急性行为敏化的发展。舒必利（50 mg/kg腹腔注射）在抑制甲基苯丙胺行为敏化方面也有效，但不影响纹状体Fos诱导。这些结果表明，多巴胺D1受体介导的机制参与了暴露于甲基苯丙胺后与行为敏化相关的纹状体Fos蛋白诱导。
