Knockdown of Piccolo in the Nucleus Accumbens Suppresses Methamphetamine-Induced Hyperlocomotion and Conditioned Place Preference in Mice
Knockdown of Piccolo in the Nucleus Accumbens Suppresses Methamphetamine-Induced Hyperlocomotion and Conditioned Place Preference in Mice
复制标题
伏核中 Piccolo 的敲低可抑制甲基苯丙胺诱导的小鼠过度运动和条件性位置偏好
DOI：
10.1007/s11064-022-03680-3
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发表时间：
2022
影响因子：
4.4
通讯作者：
Nitta Atsumi
中科院分区：
文献类型：
--
作者：
Kusui Yuka;Izuo Naotaka;Uno Kyosuke;Ge Bin;Muramatsu Shin-ichi;Nitta Atsumi
甲基苯丙胺（Methamphetamine，METH）是一种分布最广的精神兴奋剂，它能异常激活大脑中的奖赏系统，诱导成瘾行为。由Pclo编码的突触前蛋白“Piccolo”被鉴定为在小鼠延髓核（NAc）中表达增强的MET应答蛋白。虽然Piccolo在多巴胺能信号传导中的生理和病理意义已被确定，但其在MET诱导的行为异常中的作用及其潜在机制仍不清楚。为了阐明这些功能，通过局部注射携带靶向Pclowere的miRNA的腺相关病毒载体产生并研究了在NAc中具有Piccolo敲低的小鼠（NAc-miPiccolo小鼠）。NAc-miPiccolo小鼠表现出抑制hypermotorization，敏化，和条件性位置偏好行为诱导的全身给药的甲基。NAc中多巴胺的过度释放在NAc-miPiccolo小鼠中在基线和对METH的响应中减少。这些结果表明，短笛在NAc参与了甲基苯丙胺诱导的行为改变，是一个候选的治疗药物成瘾的治疗目标。
Methamphetamine (METH), the most widely distributed psychostimulant, aberrantly activates the reward system in the brain to induce addictive behaviors. The presynaptic protein “Piccolo”, encoded byPclo, was identified as a METH-responsive protein with enhanced expression in the nucleus accumbens (NAc) in mice. Although the physiological and pathological significance of Piccolo has been identified in dopaminergic signaling, its role in METH-induced behavioral abnormalities and the underlying mechanisms remain unclear. To clarify such functions, mice with Piccolo knockdown in the NAc (NAc-miPiccolo mice) by local injection of an adeno-associated virus vector carrying miRNA targetingPclowere generated and investigated. NAc-miPiccolo mice exhibited suppressed hyperlocomotion, sensitization, and conditioned place preference behavior induced by systemic administration of METH. The excessive release of dopamine in the NAc was reduced in NAc-miPiccolo mice at baseline and in response to METH. These results suggest that Piccolo in the NAc is involved in METH-induced behavioral alterations and is a candidate therapeutic target for the treatment of drug addiction.
影响因子：
2.9
作者：
ABEKAWA, T;OHMORI, T;KOYAMA, T
通讯作者：
KOYAMA, T
Piccolo 作为行为可塑性和多巴胺转运蛋白内化的调节剂
DOI：
--
发表时间：
2009
期刊：
影响因子：
--
作者：
Nitta A;et al
通讯作者：
et al
影响因子：
5.3
作者：
Niwa, Minae;Nitta, Atsumi;Nabeshima, Toshitaka
通讯作者：
Nabeshima, Toshitaka