Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats
Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats
复制标题
DOI：
10.1124/jpet.109.158394
复制
发表时间：
2010-01-01
影响因子：
3.5
通讯作者：
France, Charles P.
中科院分区：
文献类型：
--
作者：
Baladi, Michelle G.;Newman, Amy H.;France, Charles P.
多巴胺（DA）D3/D2受体激动剂的辨别性刺激效应被认为是由D2受体介导的。为了保持反应，食物的获取通常受到限制，这可能会改变药物对DA系统的神经化学和行为影响。本研究在自由喂养大鼠中建立了喹吡罗刺激控制，并测试了激动剂模拟和拮抗剂减弱喹吡罗作用的能力。研究了相同的拮抗剂减弱喹吡罗诱导的哈欠和体温过低的能力。多巴胺受体激动剂阿扑吗啡和麦角脲，而不是苯丙胺和吗啡，抑制反应的喹吡罗杠杆。D3受体选择性拮抗剂N-{4-[4-（3-氨基喹啉）-1-基]-N-[2-（3-氨基喹啉）-1-基]-N-[4-（3-氨基喹啉）-1-基]-N-[（2，3-二氯苯基）-哌嗪-1-基]-反式-丁-2-烯基}-4-吡啶-2-基-苯甲酰胺盐酸盐（PG 01037）和非选择性D3/D2受体拮抗剂雷氯必利，但不被D2受体选择性拮抗剂3-[4-（4-氯苯基）-4-羟基哌啶-1-基]甲基-1H-吲哚（L-741，626）; PG 01037和雷氯必利拮抗喹吡罗这种作用的效力超过了它们拮抗喹吡罗打哈欠剂量-反应曲线上升段的效力（认为是由D3受体介导的）。L-741，626选择性拮抗喹吡罗打哈欠剂量-反应曲线的下降段，L-741，626和雷氯必利（但不包括PG 01037）均拮抗喹吡罗的低温效应（被认为是由D2受体介导的）。食物限制（10克/天/7天）显着减少quinpirole诱导的哈欠，而不影响quinpirole的歧视。许多关于DA受体激动剂的歧视研究使用食物限制的大鼠;与这些研究一起，目前使用自由喂养大鼠的实验表明，影响直接作用DA受体激动剂行为效应的喂养条件也可能对间接作用激动剂（如可卡因和安非他明）的效应产生影响。
The discriminative stimulus effects of dopamine (DA) D3/D2 receptor agonists are thought to be mediated by D2 receptors. To maintain responding, access to food is often restricted, which can alter neurochemical and behavioral effects of drugs acting on DA systems. This study established stimulus control with quinpirole in free-feeding rats and tested the ability of agonists to mimic and antagonists to attenuate the effects of quinpirole. The same antagonists were studied for their ability to attenuate quinpirole-induced yawning and hypothermia. DA receptor agonists apomorphine and lisuride, but not amphetamine and morphine, occasioned responding on the quinpirole lever. The discriminative stimulus effects of quinpirole were attenuated by the D3 receptor-selective antagonist N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide HCl (PG01037) and the nonselective D3/D2 receptor antagonist raclopride, but not by the D2 receptor-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl-1H-indole (L-741,626); the potencies of PG01037 and raclopride to antagonize this effect of quinpirole paralleled their potencies to antagonize the ascending limb of the quinpirole yawning dose-response curve (thought to be mediated by D3 receptors). L-741,626 selectively antagonized the descending limb of the quinpirole yawning dose-response curve, and both L-741,626 and raclopride, but not PG01037, antagonized the hypothermic effects of quinpirole (thought to be mediated by D2 receptors). Food restriction (10 g/day/7 days) significantly decreased quinpirole-induced yawning without affecting the quinpirole discrimination. Many discrimination studies on DA receptor agonists use food-restricted rats; together with those studies, the current experiment using free-feeding rats suggests that feeding conditions affecting the behavioral effects of direct-acting DA receptor agonists might also have an impact on the effects of indirect-acting agonists such as cocaine and amphetamine.