Smith S E, Sharp T
University of Oxford, Department of Clinical Pharmacology, Radcliffe Infirmary, UK.
Psychopharmacology (Berl). 1997 Sep;133(1):77-84. doi: 10.1007/s002130050374.
In this study, the behavioural response to dopamine D1-like receptor agonists (SKF 38393, SKF 81297 and SKF 77434) and D2-like receptor agonists (quinpirole and RU 24213), administered alone and in combination to rats treated repeatedly with electroconvulsive shock (five ECS over 10 days) or sham, was tested. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Repeated ECS (compared to sham controls) had no significant effect on the behavioural response to SKF 38393 (7.5 mg/kg s.c.), SKF 81297 (0.2 mg/kg s.c.), SKF 77434 (0.1 mg/kg s.c.), quinpirole (0.1 and 0.25 mg/kg s.c.) or RU 24213 (0.3 mg/kg s.c.), when administered alone. In contrast, repeated ECS markedly increased locomotion (activity counts and scores) induced by the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) and by co-administration of a D1-like agonist plus a D2-like agonist [SKF 38393 (7.5 mg/kg s.c.) plus quinpirole (0.25 mg/kg s.c.), SKF 81297 (0.2 mg/kg s.c.) plus quinpirole (0.1 mg/kg s.c), and SKF 77434 (0.1 mg/kg s.c.) plus RU 24213 (0.3 mg/kg s.c.)]. This ECS-induced enhancement of dopamine-mediated behaviour was observed for up to 3 weeks after cessation of ECS treatment. In addition, ECS also enhanced the locomotor response to intra-accumbens SKF 38393 plus quinpirole (0.4 and 1.0 microgram/side, respectively). These results provide evidence that the enhancement of dopamine function by repeated ECS requires concomitant stimulation of both D1-like and D2-like receptors, and that this effect is long-lasting.
在本研究中,测试了多巴胺D1样受体激动剂(SKF 38393、SKF 81297和SKF 77434)以及D2样受体激动剂(喹吡罗和RU 24213)单独给药及联合给药时,对反复接受电惊厥休克治疗(10天内进行5次电惊厥休克)或假手术处理的大鼠的行为反应。通过自动活动计以及使用清单评分法进行直接观察来监测激动剂诱导的行为。单独给药时,反复电惊厥休克(与假手术对照组相比)对大鼠对SKF 38393(皮下注射7.5 mg/kg)、SKF 81297(皮下注射0.2 mg/kg)、SKF 77434(皮下注射0.1 mg/kg)、喹吡罗(皮下注射0.1和0.25 mg/kg)或RU 24213(皮下注射0.3 mg/kg)的行为反应无显著影响。相反,反复电惊厥休克显著增加了非选择性多巴胺激动剂阿扑吗啡(皮下注射0.5 mg/kg)以及联合给予D1样激动剂和D2样激动剂[SKF 38393(皮下注射7.5 mg/kg)加喹吡罗(皮下注射0.25 mg/kg)、SKF 81297(皮下注射0.2 mg/kg)加喹吡罗(皮下注射0.1 mg/kg)以及SKF 77434(皮下注射0.1 mg/kg)加RU 24213(皮下注射0.3 mg/kg)]所诱导的运动(活动计数和评分)。在电惊厥休克治疗停止后长达3周内均观察到这种电惊厥休克诱导的多巴胺介导行为的增强。此外,电惊厥休克还增强了对伏隔核内SKF 38393加喹吡罗(分别为每侧0.4和1.0微克)的运动反应。这些结果证明,反复电惊厥休克增强多巴胺功能需要同时刺激D1样和D2样受体,并且这种效应是持久的。