Minematsu N
Department of Neuropsychiatry, Yamaguchi University School of Medicine, Ube, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1995 Jun;15(3):247-52.
The present study was conducted to investigate the effects of chronic treatment with apomorphine on yawning and stereotyped behaviors induced by apomorphine, and catalepic responses induced by haloperidol. Rats received apomorphine (1 mg/kg, sc), a direct dopamine D1/D2 agonist, or vehicle once a day for 21 days. The chronic treatment with apomorphine shifted to the right the dose response curve of yawning to administration of apomorphine, which preferentially activates presynaptic dopamine D-2 receptors (auto receptors) at low doses. Haloperidol (0.5 mg/kg, ip)-induced catalepsy mediated by the inhibition of postsynaptic D-2 receptors was unaltered. A subsequent challenge dose of apomorphine (5 mg/kg, ip) produced oral stereotyped behaviors such as sniffing, licking and biting in the vehicle-treated rats. Chronic apomorphine treatment produced significant enhancement of sniffing alone, which may be behavioral sensitization to apomorphine, and, in contrast, attenuated licking and biting, which depend on D-2 receptor activities. These phenomena lasted for at least 30 days. Sniffing might involve relatively increased stimulation of D-1 receptors, as compared with licking and biting. These results suggest that chronic apomorphine reduces presynaptic dopamine D-2 receptor activity, and as a consequence may induce long-lasting postsynaptic dopamine receptor (mainly D-1 receptor) activation.
本研究旨在探讨阿扑吗啡长期治疗对阿扑吗啡诱导的呵欠和刻板行为以及氟哌啶醇诱导的僵住反应的影响。大鼠每天接受一次阿扑吗啡(1mg/kg,皮下注射),一种直接的多巴胺D1/D2激动剂,或赋形剂,持续21天。阿扑吗啡的长期治疗使呵欠对阿扑吗啡给药的剂量反应曲线右移,阿扑吗啡在低剂量时优先激活突触前多巴胺D-2受体(自身受体)。氟哌啶醇(0.5mg/kg,腹腔注射)通过抑制突触后D-2受体介导的僵住反应未发生改变。随后给予阿扑吗啡(5mg/kg,腹腔注射)激发剂量,在接受赋形剂治疗的大鼠中产生了诸如嗅、舔和咬等口腔刻板行为。长期阿扑吗啡治疗仅使嗅显著增强,这可能是对阿扑吗啡的行为敏化,相反,减弱了依赖D-2受体活性的舔和咬行为。这些现象持续至少30天。与舔和咬相比,嗅可能涉及相对增加的D-1受体刺激。这些结果表明,长期阿扑吗啡降低突触前多巴胺D-2受体活性,因此可能诱导持久的突触后多巴胺受体(主要是D-1受体)激活。