Sensitizing regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) elicit enduring and differential structural alterations in the brain motive circuit of the rat.
Sensitizing regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) elicit enduring and differential structural alterations in the brain motive circuit of the rat.
复制标题
DOI：
10.1016/j.neuroscience.2009.02.025
复制
发表时间：
2009-05-05
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.;Fortenberry, E.;Rebec, G. V.
反复、间歇性地暴露于精神兴奋剂安非他明和可卡因会诱导其运动激活效应的渐进性和持久性增强，称为行为敏化，这伴随着皮质纹状体神经元树突结构的类似稳定适应。我们研究了反复暴露于日益滥用的安非他明衍生物3，4-亚甲二氧基甲基安非他明（MDMA;摇头丸）是否也会导致中皮层（内侧前额叶皮层）和腹侧纹状体（核神经元）神经元的长期行为和形态学变化。大鼠连续3天每天注射2次5.0 mg/kg（±）-MDMA或生理盐水溶剂，间隔约6小时，随后4天停药，共3周。4周停药期后，MDMA预处理的大鼠表现出行为敏化，以及棘密度和多头棘数目的大幅增加，在中央棘神经元的核心和壳亚区的丘脑核。在内侧前额叶皮层，前边缘亚区显示增加的棘密度的第V层锥体神经元的远端树突，而前扣带亚区显示的树突材料的分布的变化，而不是。总的来说，我们的研究结果表明，持久的运动敏化MDMA伴随着边缘皮质纹状体电路突触连接的重组。此外，皮质亚区的差异可塑性表明，药物诱导的结构变化是不均匀的，可能是特定的电路潜在的长期变化的药物寻求和服用药物的行为。
Repeated, intermittent exposure to the psychomotor stimulants amphetamine and cocaine induces a progressive and enduring augmentation of their locomotor-activating effects, known as behavioral sensitization, which is accompanied by similarly stable adaptations in the dendritic structure of cortico-striatal neurons. We examined whether repeated exposure to the increasingly abused amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) also results in long-lasting behavioral and morphological changes in mesocortical (medial prefrontal cortex) and ventral striatal (nucleus accumbens) neurons. Rats received 2 daily injections of either 5.0 mg/kg (±)-MDMA or saline vehicle, ~6 hr apart, for 3 consecutive days, followed by 4 drug-free days for a total of 3 weeks. Following a 4-week drug-free period, MDMA-pretreated rats displayed behavioral sensitization, as well as large increases in spine density and the number of multiple-headed spines on medium spiny neurons in core and shell subregions of nucleus accumbens. In medial prefrontal cortex, the prelimbic subregion showed increased spine density on distal dendrites of layer V pyramidal neurons, while the anterior cingulate subregion showed a change in the distribution of dendritic material instead. Collectively, our results show that long-lasting locomotor sensitization to MDMA is accompanied by reorganization of synaptic connectivity in limbic-cortico-striatal circuitry. The differential plasticity in cortical subregions, moreover, suggests that drug-induced structural changes are not homogeneous and may be specific to the circuitry underlying long-term changes in drug-seeking and drug-taking behavior.
登录
查看更多内容
影响因子：
4.2
作者：
BEARDSLEY, PM;BALSTER, RL;HARRIS, LS
通讯作者：
HARRIS, LS
影响因子：
2.7
作者：
Comery, TA;Stamoudis, CX;Greenough, WT
通讯作者：
Greenough, WT
影响因子：
5
作者：
Hedou, G;Feldon, J;Heidbreder, CA
通讯作者：
Heidbreder, CA
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