Mizuki Y, Ushijima I, Yamada M
Department of Neuropsychiatry, Yamaguchi University School of Medicine, Japan.
Pharmacol Biochem Behav. 1996 Feb;53(2):437-40. doi: 10.1016/0091-3057(95)02014-4.
The influence of chronic treatment of mice with methamphetamine, an indirect dopamine agonist, on the cataleptic effects of R-(+)-chloro-2,3,4,5,-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin -7ol hydrochloride (SCH23390), a D1 receptor agonist, or haloperidol, a mainly D2 antagonist, was investigated. Once every other day treatment with 3 mg/kg SC methamphetamine for 15 days resulted in an increase in the catalepsy produced by haloperidol (0.3 mg/kg IP) (haloperidol catalepsy), but in a decrease in the catalepsy produced by SCH23390 (0.3 mg/kg IP) (SCH23390 catalepsy), 24 h and 7 days after withdrawal of methamphetamine. These effects of chronic methamphetamine were antagonized by coadministration of either SCH23390 (0.5 mg/kg SC) or haloperidol (1.0 mg/kg SC). These results suggest that the decreased responsiveness to SCH23390 in chronic methamphetamine-pretreated mice results from a supersensitivity of D1 receptors, and that the increased responsiveness to haloperidol catalepsy results from a subsensitivity of D2 receptors. The attenuated response to SCH23390 may be interpreted as an example of sensitization to methamphetamine, and the enhanced haloperidol response as an example of tolerance to methamphetamine, based on the development of supersensitivity and subsensitivity of D1 and D2 receptors, respectively, after chronic methamphetamine administration. Furthermore, it is suggested that coadministration of either SCH23390 or haloperidol could prevent the development of D1 receptor supersensitivity and D2 receptor subsensitivity induced by chronic methamphetamine.
研究了用间接多巴胺激动剂甲基苯丙胺对小鼠进行长期处理，对D1受体激动剂R-(+)-氯-2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7醇盐酸盐（SCH23390）或主要为D2拮抗剂的氟哌啶醇的僵住效应的影响。每隔一天以3mg/kg皮下注射甲基苯丙胺，持续15天，导致在停用甲基苯丙胺后24小时和7天时，氟哌啶醇（0.3mg/kg腹腔注射）产生的僵住效应（氟哌啶醇僵住效应）增强，但SCH23390（0.3mg/kg腹腔注射）产生的僵住效应（SCH23390僵住效应）减弱。慢性甲基苯丙胺的这些效应可被SCH23390（0.5mg/kg皮下注射）或氟哌啶醇（1.0mg/kg皮下注射）的共同给药所拮抗。这些结果表明，慢性甲基苯丙胺预处理小鼠对SCH23390反应性降低是由于D1受体超敏，而对氟哌啶醇僵住效应反应性增加是由于D2受体低敏。基于慢性给予甲基苯丙胺后分别出现的D1和D2受体超敏和低敏的发展，对SCH23390反应减弱可被解释为对甲基苯丙胺敏感化的一个例子，而氟哌啶醇反应增强可被解释为对甲基苯丙胺耐受的一个例子。此外，提示SCH23390或氟哌啶醇的共同给药可预防慢性甲基苯丙胺诱导的D1受体超敏和D2受体低敏的发展。
