Repeated exposure to methamphetamine, cocaine or morphine induces augmentation of dopamine release in rat mesocorticolimbic slice co-cultures.
Repeated exposure to methamphetamine, cocaine or morphine induces augmentation of dopamine release in rat mesocorticolimbic slice co-cultures.
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DOI：
10.1371/journal.pone.0024865
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Nakagawa T;Suzuki Y;Nagayasu K;Kitaichi M;Shirakawa H;Kaneko S
重复间歇性暴露于精神兴奋剂和吗啡导致其运动激活作用在啮齿动物中的逐步增强。越来越多的证据表明，中脑皮质边缘多巴胺能神经元，从腹侧被盖区的投射到延髓核和内侧前额叶皮层，在行为敏化的关键参与。在这里，我们研究了急性和慢性的影响，精神兴奋剂和吗啡对多巴胺的释放在重建的mesocorticolimbic系统包括一个大鼠三器官切片共培养的腹侧被盖区，nucleus numbens和内侧前额叶皮层区域。酪氨酸羟化酶阳性胞体位于腹侧被盖区，其突起投射到中脑前额叶核和内侧前额叶皮质区。用甲基苯丙胺（0.1-1000 µM）、可卡因（0.1-300 µM）或吗啡（0.1-100 µM）急性处理30分钟，以浓度依赖性方式增加细胞外多巴胺水平，而3，4-亚甲二氧基苯丙胺（0.1-1000 µM）几乎没有影响。每天重复暴露于甲基苯丙胺（10 µM）30分钟，持续6天后，多巴胺释放在30分钟治疗期间逐渐增加。多巴胺释放的增加，即使在甲基苯丙胺停药7天后仍保持不变。重复暴露于可卡因（1-300 µM）或吗啡（10和100 µM）也观察到类似的增加。此外，甲基苯丙胺诱导的多巴胺释放增加被NMDA受体拮抗剂MK-801（10 µM）阻止，并且在排除内侧前额叶皮层切片的双切片共培养物中未观察到。这些结果表明，重复的精神兴奋剂或吗啡诱导的多巴胺释放，即多巴胺能致敏增强，在大鼠三器官型切片共培养再现。此外，脑片共培养系统显示，NMDA受体和内侧前额叶皮层在多巴胺能敏化中起重要作用。这种体外致敏模型为研究药物滥用行为致敏机制提供了一种独特的方法。
Repeated intermittent exposure to psychostimulants and morphine leads to progressive augmentation of its locomotor activating effects in rodents. Accumulating evidence suggests the critical involvement of the mesocorticolimbic dopaminergic neurons, which project from the ventral tegmental area to the nucleus accumbens and the medial prefrontal cortex, in the behavioral sensitization. Here, we examined the acute and chronic effects of psychostimulants and morphine on dopamine release in a reconstructed mesocorticolimbic system comprised of a rat triple organotypic slice co-culture of the ventral tegmental area, nucleus accumbens and medial prefrontal cortex regions. Tyrosine hydroxylase-positive cell bodies were localized in the ventral tegmental area, and their neurites projected to the nucleus accumbens and medial prefrontal cortex regions. Acute treatment with methamphetamine (0.1–1000 µM), cocaine (0.1–300 µM) or morphine (0.1–100 µM) for 30 min increased extracellular dopamine levels in a concentration-dependent manner, while 3,4-methylenedioxyamphetamine (0.1–1000 µM) had little effect. Following repeated exposure to methamphetamine (10 µM) for 30 min every day for 6 days, the dopamine release gradually increased during the 30-min treatment. The augmentation of dopamine release was maintained even after the withdrawal of methamphetamine for 7 days. Similar augmentation was observed by repeated exposure to cocaine (1–300 µM) or morphine (10 and 100 µM). Furthermore, methamphetamine-induced augmentation of dopamine release was prevented by an NMDA receptor antagonist, MK-801 (10 µM), and was not observed in double slice co-cultures that excluded the medial prefrontal cortex slice. These results suggest that repeated psychostimulant- or morphine-induced augmentation of dopamine release, i.e. dopaminergic sensitization, was reproduced in a rat triple organotypic slice co-cultures. In addition, the slice co-culture system revealed that the NMDA receptors and the medial prefrontal cortex play an essential role in the dopaminergic sensitization. This in vitro sensitization model provides a unique approach for studying mechanisms underlying behavioral sensitization to drugs of abuse.
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影响因子：
2.5
作者：
Cass, WA;Manning, MW;Dugan, MT
通讯作者：
Dugan, MT
影响因子：
2.5
作者：
FALLON, JH;MOORE, RY
通讯作者：
MOORE, RY
DOI：
10.1186/1471-2210-6-6
发表时间：
2006-03-03
期刊：
BMC pharmacology
影响因子：
--
作者：
Han DD;Gu HH
通讯作者：
Gu HH
影响因子：
3.3
作者：
Cador, M;Bjijou, Y;Stinus, L
通讯作者：
Stinus, L
影响因子：
3.6
作者：
Gifford, AN;Park, MH;Volkow, ND
通讯作者：
Volkow, ND