Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats
Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats
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DOI：
10.1007/s00213-005-0197-y
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发表时间：
2006-01-01
影响因子：
3.4
通讯作者：
Cunningham, KA
中科院分区：
文献类型：
--
作者：
Filip, M;Bubar, MJ;Cunningham, KA
血清素（5-羟色胺; 5-羟色胺（5-HT）5-HT 2受体（5-HT 2 R）家族是可卡因行为反应性的重要调节因子，本研究分析了5-HT 2 R各亚型的作用（5-HT2AR，5-HT2BR，和5-HT_2CR）在可卡因辨别刺激效应中的作用（10 mg/kg）从生理盐水中在两个杠杆，水强化FR 20任务中，并且我们研究了5-HT 2AR拮抗剂1（Z）-[2-（二甲氨基）乙氧亚氨基]-1（2-氟苯基）-3-（4-羟基苯基）-2（E）-丙烯（SR 46349 B），5-HT 2BR拮抗剂N-（1-甲基-5-吲哚基）-N '-（3-甲基-5-异噻唑基）脲（SB 204741）和5-HT 2CR拮抗剂[（+）-顺式-4，5，7a，8，9，10，11，11 a-八氢-7H-10-甲基吲哚并（1，7-bC）（2，6）萘啶（SDZ SER-082）替代或调节可卡因的刺激作用。SR 46349 B预处理SDZ SER-082（0.5-1 mg/kg）使可卡因的剂量-反应曲线左移; SB 204741（1-3 mg/kg）无活性。我们对5-HT_2AR、5-HT_2BR和5-HT_2CR选择性拮抗剂的药理学分析表明5-HT_2AR和5-HT_2CR对可卡因刺激作用的相反影响，排除了5-HT_2BR的作用。这些数据表明，5-HT 2AR和5-HT 2CR可能是重要的调节可卡因在人类的主观影响。
The serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor (5-HT2R) family is an important regulator of the behavioral responsiveness to cocaine.The present study is an analysis of the role of the 5-HT2R subtypes (5-HT2AR, 5-HT2BR, and 5-HT2CR) in the discriminative stimulus effects of cocaine.Male Wistar rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task, and we investigated the ability of the 5-HT2AR antagonist 1(Z)-[2-(dimethylamino)ethoxyimino]-1(2-fluorophenyl)-3-(4-hydroxyphenyl)-2(E)-propene (SR 46349B), the 5-HT2BR antagonist N-(1-methyl-5-indolyl)-N'-(3-methyl-5-isothiazolyl) urea (SB 204741), and the 5-HT2CR antagonist [(+)-cis -4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo(1,7-bC)(2,6)naphthyridine (SDZ SER-082) to substitute for or to modulate the stimulus effects of cocaine.Pretreatment with SR 46349B (0.5-1 mg/kg) resulted in a rightward shift of the cocaine dose-response curve, while SDZ SER-082 (1 mg/kg) shifted the dose-response for cocaine to the left; SB 204741 (1-3 mg/kg) was inactive.Our pharmacological analyses of selective antagonists of 5-HT2AR, 5-HT2BR, and 5-HT2CR indicate oppositional influence of 5-HT2AR and 5-HT2CR on the stimulus effects of cocaine and exclude a role for the 5-HT2BR. These data suggest that 5-HT2AR and 5-HT2CR may be important in modulating the subjective effects of cocaine in humans.