Minematsu N, Ushijima I, Obara N, Mizuki Y, Yamada M
Department of Neuropsychiatry, Yamaguchi University School of Medicine, Ube, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1994 Feb;14(1):27-32.
In this study, cocaine (5-20 mg/kg), an indirect dopamine agonist, increased locomotor activity and rearing accompanied with head circling and body shaking in a dose-dependent manner. A high dose of cocaine (40 mg/kg), meaning a toxic dose, slightly induced sniffing and licking. Both SCH23390, a D-1 receptor antagonist, and raclopride, a D-2 antagonist, inhibited all behaviors induced by cocaine, suggesting that the behavioral actions of cocaine may involve the activation of D-1 and D-2 receptors. Selective D-2 agonist quinpirole (0.1 and 1.0 mg/kg) inhibited hyperlocomotion induced by cocaine (20 mg/kg), but was replaced by the typical stereotyped behaviors such as sniffing at low dose (0.1 mg/kg), and licking and gnawing at high dose (1.0 mg/kg). SK & F38393, a selective D-1 agonist, in combination of cocaine did not induce these stereotyped behaviors which resulted in synergistic interaction of D-1 and D-2 receptor stimulation. These results suggest that the indirect stimulation of postsynaptic D-2 receptors by cocaine (20 mg/kg) was insufficient to induce stereotyped behaviors. The actions of cocaine on dopamine D-1 receptors seem to be more potent than that on D-2 receptors.
在本研究中,间接多巴胺激动剂可卡因(5 - 20毫克/千克)以剂量依赖性方式增加运动活性和竖毛行为,并伴有头部转圈和身体颤抖。高剂量可卡因(40毫克/千克),即中毒剂量,轻微诱导嗅舔行为。D-1受体拮抗剂SCH23390和D-2拮抗剂雷氯必利均抑制可卡因诱导的所有行为,这表明可卡因的行为作用可能涉及D-1和D-2受体的激活。选择性D-2激动剂喹吡罗(0.1和1.0毫克/千克)抑制可卡因(20毫克/千克)诱导的运动亢进,但在低剂量(0.1毫克/千克)时被典型的刻板行为如嗅舔所取代,在高剂量(1.0毫克/千克)时被舔咬所取代。选择性D-1激动剂SK & F38393与可卡因联合使用不会诱导这些刻板行为,这导致D-1和D-2受体刺激的协同相互作用。这些结果表明,可卡因(20毫克/千克)对突触后D-2受体的间接刺激不足以诱导刻板行为。可卡因对多巴胺D-1受体的作用似乎比对D-2受体的作用更强。