Drug seeking in response to a priming injection of MDMA in rats: relationship to initial sensitivity to self-administered MDMA and dorsal striatal dopamine
Drug seeking in response to a priming injection of MDMA in rats: relationship to initial sensitivity to self-administered MDMA and dorsal striatal dopamine
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DOI：
10.1017/s1461145710000283
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发表时间：
2010-11-01
影响因子：
4.8
通讯作者：
Schenk, Susan
中科院分区：
文献类型：
--
作者：
Colussi-Mas, Joyce;Wise, Richard J.;Schenk, Susan
在实验室动物中，暴露于3，4-亚甲二氧基甲基苯丙胺（MDMA）的引发注射，在MDMA自我给药消失后产生药物寻求。本研究旨在评估药物寻求的程度是否与获得MDMA自我给药的潜伏期和纹状体多巴胺增加有关，如通过体内微透析测量的。大鼠每天接受MDMA自我给药，直到它们获得总共240次输注（总摄入量为165 mg/kg MDMA）。20只大鼠中有12只在研究的时间范围内获得自我给药，达到标准的潜伏期范围为9 d至37 d。实验者注射MDMA（10.0 mg/kg i. p.）在这些大鼠中产生了药物寻求，并且反应的数量显著高于未能满足标准的大鼠或被动接受药物的对照组大鼠产生的反应。对于符合标准的大鼠，药物寻求与自我管理的天数呈负相关，与MDMA在背侧纹状体产生的多巴胺呈正相关。重要的是，MDMA产生的多巴胺溢出对于符合标准的大鼠更大。这些研究结果表明，药物寻求的影响，最初的敏感性MDMA的增强效果和药物产生的纹状体多巴胺增加。
In laboratory animals, exposure to priming injections of 3,4-methylenedioxymethamphetamine (MDMA) produced drug seeking following extinction of MDMA self-administration. This study aimed to evaluate whether the magnitude of drug seeking was related to latency to acquisition of MDMA self-administration and increases in striatal dopamine, as measured by in-vivo microdialysis. Rats were given daily access to MDMA self-administration until they earned a total of 240 infusions (total intake of 165 mg/kg MDMA). Twelve of the 20 rats acquired self-administration within the temporal limits of the study and the latency to meet the criterion ranged from 9 d to 37 d. An experimenter-administered injection of MDMA (10.0 mg/kg i.p.) produced drug seeking in these rats, and the number of responses was significantly higher than responses produced by rats that failed to meet the criterion or by yoked control rats that received the drug passively. For rats that met the criterion, drug seeking was negatively correlated with the number of days to self-administer the criterion number of MDMA infusions and positively correlated with MDMA-produced dopamine in the dorsal striatum. Importantly, MDMA-produced dopamine overflow was greater for the rats that met the criterion. These findings suggest that drug seeking is influenced by initial sensitivity to the reinforcing effects of MDMA and to drug-produced increases in striatal dopamine.