Characterization of the discriminative stimulus effects of lorcaserin in rats.
Characterization of the discriminative stimulus effects of lorcaserin in rats.
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DOI：
10.1002/jeab.222
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发表时间：
2016-09
影响因子：
2.7
通讯作者：
France, Charles P.
中科院分区：
文献类型：
--
作者：
Serafine, Katherine M.;Rice, Kenner C.;France, Charles P.
氯酪蛋白被美国食品和药物管理局批准用于治疗肥胖症，目前正在考虑用于治疗物质使用障碍；它在5-羟色胺(5-HT)2C受体上具有激动剂特性，在其他5-羟色胺受体亚型也可能具有激动剂特性。本研究采用药物鉴别法探讨氯酪蛋白的作用机理(S)。雄性SD大鼠辨别剂量为0.56 mg/kg。生理盐水中的氯酪蛋白，同时在固定比例5的食物时间表下做出反应。氯酪蛋白(0.178-1 mg/kg)可剂量依赖性地增加氯酪蛋白水平反应。5-HT2C受体激动剂mCPP和5-HT2A受体激动剂DOM分别在8只大鼠中7只引起90%以上的氯酪蛋白反应。5-HT1a受体激动剂8-OH-DPAT在7只大鼠中有4只引起90%以上的氯酪蛋白水平反应。5-HT2C受体选择性拮抗剂SB 242084可减弱所有8只大鼠的氯酪蛋白水平反应，5-HT2A受体选择性拮抗剂MDL 100907可使7只大鼠中6只大鼠的氯酪蛋白水平反应减弱。这些结果表明，除了5-HT2C受体的激动剂特性外，氯酪蛋白还具有5-HT2A型和5HT1A型受体的激动型特性。由于一些具有5-HT2A受体激动剂特性的药物被滥用，在考虑其治疗物质使用障碍的潜力的同时，充分了解氯酪蛋白的行为影响是很重要的。
Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178–1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully understand the behavioral effects of lorcaserin while considering its potential for treating substance use disorders.
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影响因子：
3.5
作者：
Ullrich, T;Rice, KC
通讯作者：
Rice, KC
影响因子：
7.6
作者：
Higgins, Guy A.;Silenieks, Leo B.;Fletcher, Paul J.
通讯作者：
Fletcher, Paul J.
影响因子：
2.7
作者：
Navarra, Rachel;Comery, Thomas A.;Day, Mark
通讯作者：
Day, Mark
影响因子：
1.6
作者：
Stolerman IP;Childs E;Ford MM;Grant KA
通讯作者：
Grant KA
DOI：
10.1124/jpet.110.172247
发表时间：
2010-12-01
影响因子：
3.5
作者：
Fantegrossi, W. E.;Simoneau, J.;Woods, J. H.
通讯作者：
Woods, J. H.