Horita A, Carino M A, Nishimura Y
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
Life Sci. 1991;49(8):595-601. doi: 10.1016/0024-3205(91)90258-d.
SKF 38393 (5 mg/kg), but not quinpirole, shortened the duration of loss of righting reflex produced in pentobarbital-narcotized rats. This effect was blocked by atropine (2 mg/kg), but not by atropine methylbromide, suggesting involvement of central cholinergic mechanisms. The analeptic effect was also blocked by SCH 23390 (0.2 mg/kg) or raclopride (2 mg/kg). SKF 38393 also increased sodium dependent high affinity choline uptake (HACU) in cortical and hippocampal synaptosomes that had been depressed by pentobarbital. SCH 23390 or raclopride prevented the SKF 38393 reversal of the depressed HACU, indicating that both D1 and D2 mechanisms were involved mediating the analeptic effect. These results provide neurochemical evidence that cortical and hippocampal D1-mediated cholinergic activation results in a behavioral arousal (analeptic) response. They also suggest that DA mechanisms may be involved in regulation of cortical and hippocampal cholinergic neurons.
SKF 38393（5毫克/千克）可缩短戊巴比妥麻醉大鼠的翻正反射消失持续时间，而喹吡罗则无此作用。阿托品（2毫克/千克）可阻断此效应，而甲基溴化阿托品则不能，提示中枢胆碱能机制参与其中。此兴奋作用也可被SCH 23390（0.2毫克/千克）或雷氯必利（2毫克/千克）阻断。SKF 38393还可增加戊巴比妥抑制的皮质和海马突触体中钠依赖性高亲和力胆碱摄取（HACU）。SCH 23390或雷氯必利可阻止SKF 38393对受抑制的HACU的逆转，表明D1和D2机制均参与介导兴奋作用。这些结果提供了神经化学证据，表明皮质和海马中D1介导的胆碱能激活可导致行为觉醒（兴奋）反应。它们还提示多巴胺机制可能参与皮质和海马胆碱能神经元的调节。
