Williams J E, Sutherland J V, Woolverton W L
Department of Psychiatry, Pritzker School of Medicine, University of Chicago, Illinois 60637.
Behav Neural Biol. 1990 May;53(3):378-92. doi: 10.1016/0163-1047(90)90254-4.
Recent research has suggested that there is a synergistic interaction between D1 and D2 dopamine (DA) receptors and that D1 stimulation by endogenous DA is necessary for the expression of some D2-mediated behavioral effects. The purpose of the present experiment was to examine further the interactions between D1 and D2 receptors using drug discrimination (DD), a behavioral paradigm that is sensitive and selective for D1 and D2 agonist and antagonist activity. Two groups of male Sprague-Dawley rats (N = 8/group) were trained to discriminate the D2 agonist quinpirole (QUIN; either 0.05 or 0.012 mg/kg, ip, 10 min pre-session) from saline (1.0 ml/kg, ip, 10 min pre-session) in a two-lever, food-reinforced DD paradigm. QUIN (0.0015-0.1 mg/kg) produced a dose-related increase in QUIN-appropriate responding in both groups of rats. The D1 agonist SKF 38393 (SKF; 6.4-12.8 mg/kg, ip) given alone did not substitute for QUIN in either of the two training dose groups. The administration of SKF 30 min before QUIN had no effect on the QUIN dose-response function in either group of rats. These results indicate that stimulation of D1 receptors failed to potentiate a behavioral effect mediated by D2 receptors. The D1 antagonist SCH 23390 (SCH; 0.0015-0.05 mg/kg, ip) partially substituted for QUIN in the group trained with the 0.05 dose of QUIN, and to a larger extent in the group trained with the 0.012 dose of QUIN. SCH did not alter the effect of the training dose of QUIN except at a dose high enough to virtually eliminate lever pressing in the group trained to discriminate the high dose of QUIN. The failure of SCH to block QUIN suggests that D1 receptor stimulation by endogenous DA is not necessary for this D2 effect to be expressed. These results may be accounted for by assuming a presynaptic site of action for QUIN in the QUIN discrimination. Further, they demonstrate that the interaction between D1 and D2 receptors cannot be simply characterized as synergistic.
近期研究表明，多巴胺（DA）D1和D2受体之间存在协同相互作用，并且内源性DA对D1的刺激对于某些D2介导的行为效应的表达是必要的。本实验的目的是使用药物辨别（DD）进一步研究D1和D2受体之间的相互作用，DD是一种对D1和D2激动剂及拮抗剂活性敏感且具有选择性的行为范式。两组雄性Sprague-Dawley大鼠（每组N = 8）在双杠杆、食物强化的DD范式中接受训练，以辨别D2激动剂喹吡罗（QUIN；0.05或0.012 mg/kg，腹腔注射，训练前10分钟）和生理盐水（1.0 ml/kg，腹腔注射，训练前10分钟）。QUIN（0.0015 - 0.1 mg/kg）在两组大鼠中均产生了与剂量相关的QUIN适应性反应增加。单独给予D1激动剂SKF 38393（SKF；6.4 - 12.8 mg/kg，腹腔注射）在两个训练剂量组中均不能替代QUIN。在QUIN给药前30分钟给予SKF对两组大鼠的QUIN剂量反应函数均无影响。这些结果表明，刺激D1受体未能增强由D2受体介导的行为效应。D1拮抗剂SCH 23390（SCH；0.0015 - 0.05 mg/kg，腹腔注射）在以0.05剂量的QUIN训练的组中部分替代了QUIN，在以0.012剂量的QUIN训练的组中替代程度更大。除了在足以几乎消除辨别高剂量QUIN组中的杠杆按压的高剂量下，SCH并未改变训练剂量的QUIN的效果。SCH未能阻断QUIN表明内源性DA对D1受体的刺激对于该D2效应的表达不是必需的。这些结果可以通过假设QUIN在QUIN辨别中有一个突触前作用位点来解释。此外，它们表明D1和D2受体之间的相互作用不能简单地被描述为协同作用。
