Sustained AAV-mediated overexpression of CRF in the central amygdala diminishes the depressive-like state associated with nicotine withdrawal.
Sustained AAV-mediated overexpression of CRF in the central amygdala diminishes the depressive-like state associated with nicotine withdrawal.
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中央杏仁核中CRF的持续AAV介导的过表达降低了与尼古丁戒断相关的抑郁状态。
DOI：
10.1038/tp.2014.25
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发表时间：
2014-04-22
影响因子：
6.8
通讯作者：
Bruijnzeel AW
中科院分区：
文献类型：
--
作者：
Qi X;Shan Z;Ji Y;Guerra V;Alexander JC;Ormerod BK;Bruijnzeel AW
戒烟会导致烦躁不安，从而增加复发的风险。动物研究表明，与尼古丁戒断相关的烦躁状态至少部分是由杏仁核（CeA）中央核中促肾上腺皮质激素释放因子（CRF）释放的增加介导的。在本研究中，我们研究了 CeA 中 CRF 的持续过度表达是否会影响与尼古丁戒断相关的烦躁状态。为了研究大脑奖赏功能，在大鼠的内侧前脑束中放置了颅内自刺激（ICSS）电极。使用腺相关病毒（AAV，假型 2/5）在 CeA 中过表达 CRF 或绿色荧光蛋白（GFP，对照），并使用微型泵来诱导尼古丁依赖。 AAV2/5-CRF 载体诱导 CeA 中 CRF 蛋白和 mRNA 水平增加 40%。给予烟碱受体拮抗剂美加明（突然戒断）或去除尼古丁泵（自发戒断）会导致 ICSS 阈值升高。 ICSS 阈值升高表明存在类似烦躁的状态。 CRF 的过度表达不会影响基线 ICSS 阈值，但会降低与突然和自发尼古丁戒断相关的 ICSS 阈值升高。实时逆转录酶（RT）-PCR分析表明，CRF的过表达导致CeA中CRF1 mRNA水平下降和CRF2 mRNA水平增加。总之，CeA 中 CRF 的过度表达减轻了与尼古丁戒断相关的烦躁状态，这可能是由 CRF1 和 CRF2 受体基因表达的神经适应性变化驱动的。
Smoking cessation leads to a dysphoric state and this increases the risk for relapse. Animal studies indicate that the dysphoric state associated with nicotine withdrawal is at least partly mediated by an increase in corticotropin-releasing factor (CRF) release in the central nucleus of the amygdala (CeA). In the present study, we investigated whether a sustained overexpression of CRF in the CeA affects the dysphoric-like state associated with nicotine withdrawal. To study brain reward function, rats were prepared with intracranial self-stimulation (ICSS) electrodes in the medial forebrain bundle. An adeno-associated virus (AAV, pseudotype 2/5) was used to overexpress CRF or green fluorescent protein (GFP, control) in the CeA and minipumps were used to induce nicotine dependence. The AAV2/5-CRF vector induced a 40% increase in CRF protein and mRNA levels in the CeA. Administration of the nicotinic receptor antagonist mecamylamine (precipitated withdrawal) or nicotine pump removal (spontaneous withdrawal) led to elevations in ICSS thresholds. Elevations in ICSS thresholds are indicative of a dysphoric-like state. The overexpression of CRF did not affect baseline ICSS thresholds but diminished the elevations in ICSS thresholds associated with precipitated and spontaneous nicotine withdrawal. The real-time reverse transcriptase (RT)–PCR analysis showed that the overexpression of CRF led to a decrease in CRF1 mRNA levels and an increase in CRF2 mRNA levels in the CeA. In conclusion, the overexpression of CRF in the CeA diminishes the dysphoric-like state associated with nicotine withdrawal and this might be driven by neuroadaptive changes in CRF1 and CRF2 receptor gene expression.
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DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
11.1
作者：
George, Olivier;Ghozland, Sandy;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
11
作者：
通讯作者：
--
影响因子：
3.4
作者：
Cohen A;Treweek J;Edwards S;Leão RM;Schulteis G;Koob GF;George O
通讯作者：
George O
影响因子：
2.9
作者：
CADOR, M;AHMED, SH;STINUS, L
通讯作者：
STINUS, L
影响因子：
11
作者：
Ingallinesi, M.;Rouibi, K.;Contarino, A.
通讯作者：
Contarino, A.