Neurochemical and behavioral evidence that quipazine-ketanserin discrimination is mediated by serotonin2A receptor.
Neurochemical and behavioral evidence that quipazine-ketanserin discrimination is mediated by serotonin2A receptor.
复制标题
DOI：
--
复制
发表时间：
1995-11
期刊：
影响因子：
--
通讯作者：
R. Smith;R. Barrett;E. sanders-Bush
中科院分区：
文献类型：
--
作者：
R. Smith;R. Barrett;E. sanders-Bush
本研究的目的是确定：首先，是否可以训练动物区分5-羟色胺（5-HT）2受体激动剂和5-HT2受体拮抗剂；第二，哪一种5-HT2受体亚型介导了线索；第三，该模型在研究5-HT2受体系统适应性变化方面的实用性。大鼠被训练区分喹帕嗪（0.5 mg/kg）和酮色林（1.0 mg/kg）在可变间隔-20强化时间表。采集后，喹帕嗪和酮色林的剂量-反应曲线有序，重现性好。其他5-HT2受体激动剂（2,5-二甲氧基-4-碘安非他明和MK 212）和拮抗剂（pizotifen, mianserin， pirenperone和MDL 100,907）进行了泛化测试，发现它们分别替代了喹帕嗪和酮色林线索。在拮抗剂研究中，MDL 100,907有效地阻断了喹帕嗪的鉴别。旨在评估5-HT2A和5-HT2C受体占用的离体结合研究结果表明，酮色林的训练剂量仅阻断5-HT2A受体，而不阻断5-HT2C受体。替代、拮抗和离体受体放射自显影研究的综合结果表明，喹帕嗪和酮色林的鉴别刺激至少部分是由5-HT2A受体介导的。我们还设计了其他实验来研究5-HT2A受体的适应性变化。单次大剂量喹帕嗪在给药后20小时产生类似酮色林的反弹效应；然而，单次大剂量的酮色林（10mg /kg）并没有产生类似喹帕嗪的反跳效应。
The purposes of this study were to determine: first, if animals could be trained to discriminate a serotonin (5-HT)2 receptor agonist from a 5-HT2 receptor antagonist; second, which 5-HT2 receptor subtype was mediating the cues; and third, the usefulness of this model for studying adaptive changes in the 5-HT2 receptor system. Rats were trained to discriminate quipazine (0.5 mg/kg) from ketanserin (1.0 mg/kg) on a variable interval-20 schedule of reinforcement. After acquisition, the quipazine and ketanserin dose-response curves were found to be orderly and reproducible. Additional 5-HT2 receptor agonists (2,5-dimethoxy-4-iodoamphetamine and MK 212) and antagonists (pizotifen, mianserin, pirenperone and MDL 100,907) were tested for generalization and found to substitute for the quipazine and ketanserin cues, respectively. In antagonist studies, MDL 100,907 potently blocked quipazine discrimination. Results of ex vivo binding studies designed to estimate occupancy of 5-HT2A and 5-HT2C receptors suggested that the training dose of ketanserin blocked only 5-HT2A receptors and not 5-HT2C receptors. The combined results from the substitution, antagonism and ex vivo receptor autoradiographic studies suggest that the discriminative stimuli of quipazine and ketanserin are mediated at least in part by the 5-HT2A receptor. Additional experiments were designed to study adaptive changes in the 5-HT2A receptor. A single large dose of quipazine produced a rebound ketanserin-like effect at 20 hr after administration; however, a single large dose of ketanserin (10 mg/kg) did not produce a rebound quipazine-like effect.