Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas
Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas
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DOI：
10.1016/j.pbb.2005.05.011
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发表时间：
2005-08-01
影响因子：
3.6
通讯作者：
Rabin, RA
中科院分区：
文献类型：
--
作者：
Doat-Meyerhoefer, MM;Hard, R;Rabin, RA
5-HT 2A受体的激活已被证明是吲哚胺和苯乙胺致幻剂的区别性刺激效应的重要组成部分。本研究的目的是确定可能与苯乙胺致幻剂[-] 2，5-二甲氧基-4-甲基苯丙胺（DOM）的刺激效应有关的5-HT（2A）受体的神经解剖学定位。据推测，在DOM诱导的刺激控制的类似改变的背景下，含有改变的5-HT 2A受体表达的脑区可能在介导DOM的刺激效应中是重要的。Fisher 344大鼠用氯氮平（25 mg/ kg/天）或DOM（2 mg/kg/天）治疗7天，并测定这些药物治疗方案对DOM诱导的刺激控制和几个脑区5-HT 2A受体表达的影响。长期服用氯氮平与5-HT 2A/2C受体水平的广泛降低有关。相反，DOM治疗有不同的效果，包括神经解剖学选择性降低5-HT 2A/2C受体水平，仅限于嗅核。DOM和氯氮平的慢性治疗都降低了DOM的刺激效应。目前的研究结果表明，嗅觉核在产生DOM的刺激效应的作用。(c)2005年爱思唯尔公司All rights reserved.
Activation of 5-HT2A receptors has been shown to be an essential component of the discriminative stimulus effects of indoleamine and phenethylamine hallucinogens. The objective of the present study was to determine the neuroanatomical location of the 5HT(2A) receptors which may be responsible for the stimulus effects of the phenethylamine hallucinogen [-]2,5-dimethoxy-4-methylamphetamine (DOM). It was hypothesized that brain areas containing altered 5-HT2A receptor expression in the context of a similar alteration in DOM-induced stimulus control might be important in mediating the stimulus effects of DOM. Fisher 344 rats were treated with either clozapine (25 mg/ kg/day) or DOM (2 mg/kg/day) for 7 days, and the consequences of these drug treatment regimens on DOM-induced stimulus control and on 5-HT2A receptor expression in several brain areas were determined. Chronic administration of clozapine was associated with a widespread decrease in levels of 5-HT2A/2C receptors. Conversely, treatment with DOM had varied effects including a neuroanatomically selective decrease in 5-HT2A/2C receptor levels that was restricted to the olfactory nucleus. Both chronic treatment with DOM and clozapine decreased the stimulus effects of DOM. The present findings suggest a role for the olfactory nucleus in producing the stimulus effects of DOM. (c) 2005 Elsevier Inc. All rights reserved.