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大鼠纹状体中对摇头丸(MDMA)给药的情境依赖性行为和神经元敏化

Context-dependent behavioural and neuronal sensitization in striatum to MDMA (ecstasy) administration in rats.

作者信息

Ball Kevin T, Budreau Daniel, Rebec George V

机构信息

Department of Psychological and Brain Sciences and Program in Neuroscience, Indiana University, 1101 East 10th Street, Bloomington, IN, USA.

出版信息

Eur J Neurosci. 2006 Jul;24(1):217-28. doi: 10.1111/j.1460-9568.2006.04885.x.

DOI:10.1111/j.1460-9568.2006.04885.x
PMID:16882018
Abstract

To investigate the neuronal mechanisms underlying the behavioural alterations that accompany repeated exposure to MDMA (ecstasy), we recorded the activity of > 200 striatal units in response to multiple, intermittent, locomotor-activating doses (5.0 mg/kg) of MDMA. Rats were treated with once-daily injections of either saline or MDMA for 5 days when housed in their home cage, followed by a challenge injection 3-5 days later when housed in a recording chamber. Because contextual drug associations might be particularly important to the expression of behavioural sensitization to chronic MDMA, a separate group of rats received repeated injections of MDMA alternately in the recording chamber or home cage, according to the above timeline. A sensitized locomotor response was observed only in rats that had previously experienced MDMA in the context of the recording chamber, and only on the challenge day. These sensitized animals also showed a decreased basal firing rate in neurons that were subsequently excited by MDMA when compared with the same category of neurons earlier in the treatment regimen. This resulted in a greater percentage increase from the baseline firing rate on the challenge day compared with the first and fifth days of treatment, even though this trend was not evident with an analysis of absolute firing rate. These results strongly support a role for context in the expression of MDMA-induced locomotor sensitization, and implicate striatal involvement in the neurobehavioural changes associated with the repeated use of MDMA.

摘要

为了研究反复接触摇头丸(3,4-亚甲基二氧甲基苯丙胺)所伴随行为改变的神经机制,我们记录了200多个纹状体神经元单位对多次间歇性给予的可激活运动的摇头丸剂量(5.0毫克/千克)的反应。大鼠在其饲养笼中时,每天注射一次生理盐水或摇头丸,持续5天,然后在3至5天后将其置于记录室时给予一次激发注射。由于情境性药物关联可能对慢性摇头丸行为敏化的表达尤为重要,另一组大鼠按照上述时间安排,在记录室或饲养笼中交替接受反复注射摇头丸。仅在先前于记录室环境中接触过摇头丸的大鼠身上,且仅在激发日观察到了敏化的运动反应。与治疗方案早期同一类别的神经元相比,这些出现敏化的动物中,随后被摇头丸兴奋的神经元的基础放电率也有所降低。这导致在激发日与治疗的第一天和第五天相比,基础放电率的增加百分比更大,尽管对绝对放电率的分析中这一趋势并不明显。这些结果有力地支持了情境在摇头丸诱导的运动敏化表达中的作用,并表明纹状体参与了与反复使用摇头丸相关的神经行为变化。

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