Overexpression of ASIC1A in the nucleus accumbens of rats potentiates cocaine-seeking behavior.
Overexpression of ASIC1A in the nucleus accumbens of rats potentiates cocaine-seeking behavior.
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作者：
酸敏感离子通道（ASIC）在中脑边缘皮质系统的核心核（NAcore）中大量表达，该区域在调节药物寻求行为中具有确定的作用。先前的研究表明，单剂量的可卡因降低了Asic 1a −/−小鼠中AMPA与NMDA的比例，这是在野生型小鼠中戒断后观察到的效果，而大鼠NAcore中ASIC 1A的过表达减少了可卡因的自我给药。然而，在NAcore中ASIC 1A过表达是否会改变自我给药期后的药物寻求行为的测量尚不清楚。为了研究这个问题，ASIC 1A亚基在雄性Sprague-Dawley大鼠中过表达，在完成两周的可卡因或食物自我给药后，通过注射靶向NAcore的腺相关病毒。在21天的居家禁欲后，大鼠进行了线索/上下文驱动的药物/食物寻求测试，然后进行消退训练，然后进行药物/食物启动，线索，和线索+药物/食物启动恢复测试。结果表明，ASIC 1A在NAcore中的过表达增强了线索/上下文驱动的可卡因寻求，可卡因引发的恢复和线索+可卡因引发的恢复，但对食物寻求行为没有影响，表明ASIC 1A在灭绝和可卡因寻求行为的过程中具有选择性作用。
Acid-sensing ion channels (ASICs) are abundantly expressed in the nucleus accumbens core (NAcore), a region of the mesolimbocortical system that has an established role in regulating drug-seeking behavior. Previous work shows that a single dose of cocaine reduced the AMPA-to-NMDA ratio in Asic1a−/− mice, an effect observed after withdrawal in wild-type mice, whereas ASIC1A overexpression in the NAcore of rats decreases cocaine self-administration. However, whether ASIC1A overexpression in the NAcore alters measures of drug-seeking behavior after the self-administration period is unknown. To examine this issue, the ASIC1A subunit was overexpressed in male Sprague-Dawley rats by injecting them with adeno-associated virus, targeted at the NAcore, after completion of two weeks of cocaine or food self-administration. After 21 days of homecage abstinence, rats underwent a cue-/context-driven drug/food-seeking test, followed by extinction training and then drug/food-primed, cued, and cued + drug/food-primed reinstatement tests. The results indicate that ASIC1A overexpression in the NAcore enhanced cue-/context-driven cocaine seeking, cocaine-primed reinstatement, and cued + cocaine-primed reinstatement but had no effect on food-seeking behavior, indicating a selective effect for ASIC1A in the processes underlying extinction and cocaine-seeking behavior.
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影响因子：
25
作者：
Moussawi, Khaled;Pacchioni, Alejandra;Moran, Megan;Olive, M. Foster;Gass, Justin T.;Lavin, Antonieta;Kalivas, Peter W.
通讯作者：
Kalivas, Peter W.
DOI：
10.1073/pnas.0608018103
发表时间：
2006-10-31
影响因子：
11.1
作者：
Zha, Xiang-ming;Wemmie, John A.;Welsh, Michael J.
通讯作者：
Welsh, Michael J.
影响因子：
25
作者：
Kreple, Collin J.;Lu, Yuan;Wemmie, John A.
通讯作者：
Wemmie, John A.
影响因子：
5.3
作者：
Gonzalez-Inchauspe, Carlota;Urbano, Francisco J.;Uchitel, Osvaldo D.
通讯作者：
Uchitel, Osvaldo D.
影响因子：
3.3
作者：
Jiang, Q.;Li, M. -H.;Chu, X. -P.
通讯作者：
Chu, X. -P.