Electrophysiological and structural alterations in striatum associated with behavioral sensitization to (±)3,4-methylenedioxymethamphetamine (Ecstasy) in rats: role of drug context.
Electrophysiological and structural alterations in striatum associated with behavioral sensitization to (±)3,4-methylenedioxymethamphetamine (Ecstasy) in rats: role of drug context.
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DOI：
10.1016/j.neuroscience.2010.09.041
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发表时间：
2010-12-15
期刊：
影响因子：
3.3
通讯作者：
Rebec, G. V.
中科院分区：
文献类型：
--
作者：
Ball, K. T.;Wellman, C. L.;Miller, B. R.;Rebec, G. V.
我们研究了反复暴露于日益滥用的安非他明衍生物3,4-亚甲基二氧基甲基苯丙胺（MDMA；摇头丸）是否会导致长期的神经行为改变，以及进一步，环境线索调节这些变化的能力。我们的研究重点是背纹状体，这是一个与持续吸毒习惯形成有关的大脑区域。将大鼠运送到一个新的记录室，每天注射一次（±）-MDMA （5.0 mg/kg）或生理盐水5天，然后在14天后在相同（实验1）或不同的环境（实验2）中进行激发注射。用长期植入的微丝束记录纹状体神经元在第1天、第5天和刺激时的情况。最后一次注射24小时后，取出大脑，使用改进的高尔基法处理，以评估神经元形态学的变化。实验1中，12只大鼠中有11只在MDMA刺激后出现致敏运动反应，而在实验2中，只有58%的大鼠（12只中的7只）表现出致敏反应。此外，纹状体电生理的一些变化在刺激日是明显的，但仅在表现出致敏的大鼠。相反，在mdma治疗的大鼠中，无论是否表现出行为致敏，纹状体中棘神经元的结构变化，如脊柱密度的增加，都被观察到。因此，似乎背纹状体突触连通性的重组可能有助于长期药物诱导的行为改变，但这些行为改变受到个体差异和药物施用环境的影响。
We examined whether repeated exposure to the increasingly abused amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) results in long-lasting neurobehavioral changes, and further, the ability of contextual cues to modulate these changes. We focused on dorsal striatum, a brain region implicated in the formation of persistent drug-related habits. Rats were transported to a novel recording chamber and treated with once-daily injections (sc) of (±)-MDMA (5.0 mg/kg) or saline for 5 days, followed by a challenge injection 14 days later either in the same (Experiment 1) or different context (Experiment 2). Chronically implanted micro-wire bundles were used to record from populations of striatal neurons on days 1, 5, and challenge. Twenty-four h after the last injection, brains were removed and processed using a modified Golgi method to assess changes in neuronal morphology. A sensitized locomotor response was observed following MDMA challenge in 11 of 12 rats in Experiment 1 (same context), whereas only 58% of rats (7 of 12) displayed sensitization in Experiment 2 (different context). Furthermore, several alterations in striatal electrophysiology were apparent on challenge day, but only in rats that displayed sensitization. Conversely, structural changes in striatal medium spiny neurons, such as increases in spine density, were observed in MDMA-treated rats regardless of whether they displayed behavioral sensitization. Thus, it appears that reorganization of synaptic connectivity in dorsal striatum may contribute to long-lasting drug-induced behavioral alterations, but that these behavioral alterations are subject to modification depending on individual differences and the context surrounding drug administration.
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影响因子：
3.3
作者：
Ball, K. T.;Wellman, C. L.;Fortenberry, E.;Rebec, G. V.
通讯作者：
Rebec, G. V.
影响因子：
2.7
作者：
Comery, TA;Stamoudis, CX;Greenough, WT
通讯作者：
Greenough, WT
影响因子：
1.9
作者：
Anagnostaras, SG;Robinson, TE
通讯作者：
Robinson, TE
影响因子：
4.7
作者：
BRADBERRY, CW;NOBILETTI, JB;ROTH, RH
通讯作者：
ROTH, RH
影响因子：
3
作者：
GLASER, EM;VANDERLOOS, H
通讯作者：
VANDERLOOS, H