Yoshida K, Gjerde D K, Carino M A, Halpern L M, Horita A
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
Neuropharmacology. 1993 May;32(5):487-92. doi: 10.1016/0028-3908(93)90174-2.
The effects of the dopamine D1 and D2 receptor antagonists on cocaine-induced, cholinergically-mediated analeptic and hippocampal theta activity in anesthetized rabbits were investigated. Cocaine (2 mg/kg, i.v.) reduced by 35% the duration of loss of righting reflex produced by a 25 mg/kg dose of pentobarbital. This shortening of narcosis time was blocked by pretreating the animals with the D1 antagonist, SCH 23390 (0.1 mg/kg) but not with the D2 antagonist raclopride (1-2 mg/kg). Cocaine (5 mg/kg, i.v.) also produced a short burst of increased hippocampal theta activity in urethane-anesthetized rabbits, which was also blocked by SCH 23390 but not by raclopride. An unexpected finding was that raclopride itself, at 2 mg/kg (i.v.), produced a marked activation of theta activity that lasted for 15-20 min. When cocaine was administered after this time it produced a potentiated theta response, both in duration and in magnitude. These results suggest that in the rabbit, cocaine exerts a cholinergically-mediated behavioral and EEG arousal through a D1 dopamine mechanism. The role of the D2 system is less clear but appears to be antagonistic to the D1-mediated response.
研究了多巴胺D1和D2受体拮抗剂对可卡因诱导的、胆碱能介导的麻醉兔催醒作用及海马θ波活动的影响。可卡因（2mg/kg，静脉注射）可使25mg/kg剂量戊巴比妥钠所致翻正反射消失的持续时间缩短35%。用D1拮抗剂SCH 23390（0.1mg/kg）预处理动物可阻断这种麻醉时间的缩短，但用D2拮抗剂雷氯必利（1 - 2mg/kg）预处理则不能。可卡因（5mg/kg，静脉注射）还可使氨基甲酸乙酯麻醉的兔海马θ波活动短暂增强，这一作用也被SCH 23390阻断，但未被雷氯必利阻断。一个意外的发现是，雷氯必利本身在2mg/kg（静脉注射）时可使θ波活动显著激活，持续15 - 20分钟。在此之后给予可卡因，其在持续时间和强度上均产生增强的θ波反应。这些结果表明，在兔中，可卡因通过D1多巴胺机制发挥胆碱能介导的行为和脑电图唤醒作用。D2系统的作用尚不清楚，但似乎与D1介导的反应相反。
