Agonist and antagonist activity of low efficacy D2 dopamine receptor agonists in rats discriminating d‐amphetamine from saline
Agonist and antagonist activity of low efficacy D2 dopamine receptor agonists in rats discriminating d‐amphetamine from saline
复制标题
低效 D2 多巴胺受体激动剂在区分 d-苯丙胺和生理盐水的大鼠中的激动剂和拮抗剂活性
DOI：
10.1097/00008877-199212000-00008
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发表时间：
1992
影响因子：
1.6
通讯作者：
D. Clark
中科院分区：
文献类型：
--
作者：
M. Exner;D. Clark
在经过训练区分 d-苯丙胺 (0.5 mg/kg) 和盐水的大鼠中，研究了低效 D2 激动剂 preclamol 和 SDZ 208-911 拮抗和替代 d-苯丙胺辨别线索的能力。所有剂量的 preclamol (2.0–16.0 mg/kg) 和 SDZ 208–911 (0.125–1.0 mg/kg) 仅部分拮抗 d-苯丙胺歧视。相比之下，功效较低的 D2 激动剂 SDZ 208-912 完全阻断了 d-苯丙胺的提示特性。 Preclamol（4.0 和 16.0 mg/kg）和 SDZ 208–911（1.0 mg/kg）也部分替代了 d-苯丙胺。在另一项研究中，前一种药物增强了低剂量 d-苯丙胺 (0.125 mg/kg) 的辨别作用，同时拮抗训练剂量的作用。 Preclamol 还部分拮抗选择性 D2 激动剂喹吡罗 (0.125 mg/kg) 替代 d-苯丙胺的能力。与药物辨别结果相反，在接受与药物辨别大鼠相同的长期 d-苯丙胺治疗的动物中，普克拉莫完全拮抗由急性 d-苯丙胺引起的运动亢进。目前的研究结果表明，preclamol 和 SDZ 208-911 可以在经过训练区分 d-苯丙胺和盐水的动物中发挥激动剂和拮抗剂活性。这种部分激动剂分布可能是由于低效 D2 激动剂与突触后 D2 受体群体相互作用，该群体具有比介导 d-苯丙胺诱导的运动亢进的那些 D2 受体更高的反应能力。
The ability of the low efficacy D2 agonists preclamol and SDZ 208–911 to both antagonise, and substitute for, the d-amphetamine discriminative cue was investigated in rats trained to discriminate d-amphetamine (0.5 mg/kg) from saline. All doses of preclamol (2.0–16.0 mg/kg) and SDZ 208–911 (0.125–1.0 mg/kg) only partially antagonised d-amphetamine discrimination. In contrast, the lower efficacy D2 agonist SDZ 208–912 completely blocked the cueing properties of d-amphetamine. Preclamol (4.0 and 16.0 mg/kg) and SDZ 208–911 (1.0 mg/kg) also partially substituted for d-amphetamine. In an additional study, the former drug enhanced the discriminative effects of a low dose of d-amphetamine (0.125 mg/kg), whilst antagonising the effects of the training dose. Preclamol also partially antagonised the ability of the selective D2 agonist quinpirole (0.125 mg/kg) to substitute for d-amphetamine. In contrast to the drug discrimination Findings, preclamol completely antagonised the loco-motor hyperactivity induced by acute d-amphetamine, in animals which had received the same long-term d-amphetamine treatment as the drug discrimination rats. The present findings reveal that preclamol and SDZ 208–911 can exert both agonist and antagonist activity in animals trained to discriminate d-amphetamine from saline. This partial agonist profile is probably due to the low efficacy D2 agonists interacting with a postsynaptic D2 receptor population possessing a higher response capability than those D2 receptors mediating d-amphetamine-induced locomotor hyperactivity.