SCH23390 Reduces Methamphetamine Self-Administration and Prevents Methamphetamine-Induced Striatal LTD.
SCH23390 Reduces Methamphetamine Self-Administration and Prevents Methamphetamine-Induced Striatal LTD.
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DOI：
10.3390/ijms21186491
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发表时间：
2020-09-05
影响因子：
5.6
通讯作者：
Mandyam C
中科院分区：
文献类型：
--
作者：
Avchalumov Y;Trenet W;Piña-Crespo J;Mandyam C
扩展访问甲基苯丙胺自我管理的结果在不受管制的药物摄入量，但是，背侧纹状体多巴胺D1样受体（D1 Rs）的作用，在扩展访问条件下的甲基苯丙胺的增强性能尚不清楚。急性（离体）和慢性（体内）甲基苯丙胺暴露诱导背侧纹状体，一个关键区域的神经可塑性的变化，涉及工具性学习。例如，甲基苯丙胺暴露改变高频刺激（HFS）诱导的背侧纹状体长时程抑制;然而，甲基苯丙胺对HFS诱导的背侧纹状体长时程增强（LTP）的影响尚不清楚。在目前的研究中，在广泛使用甲基苯丙胺自我给药之前，背侧纹状体输注SCH 23390（一种D1 R拮抗剂）可减少甲基苯丙胺成瘾样行为。行为减少与背侧纹状体中PSD-95表达减少有关。电生理研究结果表明，甲基苯丙胺的灌流减少背侧纹状体切片的基础突触传递和HFS诱导的LTP，SCH 23390阻止了这种效果。这些结果表明，急性甲基苯丙胺通过D1 Rs诱导的突触传递和突触可塑性的改变可以协助甲基苯丙胺诱导的皮质纹状体回路的修改，这些回路是学习目标导向的工具动作和习惯形成的基础，介导甲基苯丙胺自我管理和甲基苯丙胺成瘾样行为的升级。
Extended-access methamphetamine self-administration results in unregulated intake of the drug; however, the role of dorsal striatal dopamine D1-like receptors (D1Rs) in the reinforcing properties of methamphetamine under extended-access conditions is unclear. Acute (ex vivo) and chronic (in vivo) methamphetamine exposure induces neuroplastic changes in the dorsal striatum, a critical region implicated in instrumental learning. For example, methamphetamine exposure alters high-frequency stimulation (HFS)-induced long-term depression in the dorsal striatum; however, the effect of methamphetamine on HFS-induced long-term potentiation (LTP) in the dorsal striatum is unknown. In the current study, dorsal striatal infusion of SCH23390, a D1R antagonist, prior to extended-access methamphetamine self-administration reduced methamphetamine addiction-like behavior. Reduced behavior was associated with reduced expression of PSD-95 in the dorsal striatum. Electrophysiological findings demonstrate that superfusion of methamphetamine reduced basal synaptic transmission and HFS-induced LTP in dorsal striatal slices, and SCH23390 prevented this effect. These results suggest that alterations in synaptic transmission and synaptic plasticity induced by acute methamphetamine via D1Rs could assist with methamphetamine-induced modification of corticostriatal circuits underlying the learning of goal-directed instrumental actions and formation of habits, mediating escalation of methamphetamine self-administration and methamphetamine addiction-like behavior.
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DOI：
10.3233/bpl-190097
发表时间：
2020-12-29
期刊：
Brain plasticity (Amsterdam, Netherlands)
影响因子：
--
作者：
Avchalumov Y;Piña-Crespo JC;Woodward JJ;Mandyam CD
通讯作者：
Mandyam CD
影响因子：
2.7
作者：
Ikemoto, Satoshi;Yang, Chen;Tan, Aaron
通讯作者：
Tan, Aaron
影响因子：
6
作者：
Baicy, Kate;London, Edythe D.
通讯作者：
London, Edythe D.
影响因子：
3.6
作者：
Gu, Sun Mi;Cha, Hye Jin;Yun, Jaesuk
通讯作者：
Yun, Jaesuk
影响因子：
2.5
作者：
CALABRESI, P;MAJ, R;BERNARDI, G
通讯作者：
BERNARDI, G