Long access to cocaine self-administration dysregulates the glutamate synapse in the nucleus accumbens core of serotonin transporter knockout rats.
Long access to cocaine self-administration dysregulates the glutamate synapse in the nucleus accumbens core of serotonin transporter knockout rats.
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DOI：
10.1111/bph.15496
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发表时间：
2022-09
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
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众所周知，伏隔核和谷氨酸在滥用药物的动机中起着关键作用。我们先前已经证明，切断5-羟色胺(5-HT)转运体的大鼠(SERT−/−大鼠)表现出可卡因摄入量增加，这让人联想到强迫症。通过对SERT−/−与SERT+/+大鼠的比较，我们开始探索SERT缺失在对照条件下以及在短时间(1小时/次)或长时间(6小时/次)可卡因自我给药后是否影响谷氨酸神经递质。于给药结束后24 h处死大鼠，进行谷氨酸系统(囊泡和神经胶质转运体、NMDA型和AMPA型受体突触后亚单位及其相关支架蛋白)的体外分子分析。这样的分析是在伏隔核核心进行的。在可卡因幼稚的动物中，SERT缺失引起谷氨酸能神经传递标记物的广泛异常，总体上表明谷氨酸信号减少。这些结果表明，5-羟色胺在维持谷氨酸蓄积平衡中起着关键作用。我们还发现，SERT缺失主要在长时间接触可卡因后改变谷氨酸稳态，而不是短时间接触可卡因。我们的研究结果表明，SERT缺失可能会使伏核核心的谷氨酸能突触对可卡因的长通路而不是短通路敏感。这篇文章是关于精神和疼痛障碍的新发现和新视角的主题问题的一部分。要查看本节中的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc
It is well established that the nucleus accumbens and glutamate play a critical role in the motivation to take drugs of abuse. We have previously demonstrated that rats with ablation of the serotonin (5‐HT) transporter (SERT−/− rats) show increased cocaine intake reminiscent of compulsivity. By comparing SERT−/− to SERT+/+ rats, we set out to explore whether SERT deletion influences glutamate neurotransmission under control conditions as well as after short access (1 h/session) or long access (6 h/session) to cocaine self‐administration. Rats were killed at 24 h after the final self‐administration session for ex vivo molecular analyses of the glutamate system (vesicular and glial transporters, post‐synaptic subunits of NMDA and AMPA receptors and their related scaffolding proteins). Such analyses were undertaken in the nucleus accumbens core. In cocaine‐naïve animals, SERT deletion evoked widespread abnormalities in markers of glutamatergic neurotransmission that, overall, indicate a reduction of glutamate signalling. These results suggest that 5‐HT is pivotal for the maintenance of accumbal glutamate homeostasis. We also found that SERT deletion altered glutamate homeostasis mainly after long access, but not short access, to cocaine. Our findings reveal that SERT deletion may sensitize the glutamatergic synapses of the nucleus accumbens core to the long access but not short access, intake of cocaine. This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc
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影响因子：
13.5
作者：
Abdallah CG;Sanacora G;Duman RS;Krystal JH
通讯作者：
Krystal JH
影响因子：
5.3
作者：
McCutcheon, James E.;Wang, Xiaoting;Marinelli, Michela
通讯作者：
Marinelli, Michela
影响因子：
7.3
作者：
Caffino, Lucia;Verheij, Michel M. M.;Homberg, Judith R.
通讯作者：
Homberg, Judith R.
影响因子：
3.4
作者：
Caffino, Lucia;Verheij, Michel M. M.;Fumagalli, Fabio
通讯作者：
Fumagalli, Fabio
影响因子：
3.4
作者：
Giannotti, Giuseppe;Caffino, Lucia;Fumagalli, Fabio
通讯作者：
Fumagalli, Fabio