Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals.
Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals.
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DOI：
10.1016/j.pnpbp.2021.110334
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发表时间：
2021-12-20
影响因子：
5.6
通讯作者：
Sala M
中科院分区：
文献类型：
--
作者：
Ponzoni L;Melzi G;Marabini L;Martini A;Petrillo G;Teh MT;Torres-Perez JV;Morara S;Gotti C;Braida D;Brennan CH;Sala M
尼古丁戒断综合征是一个主要的临床问题。缺乏具有足够预测有效性的动物模型，以支持临床前研究结果转化为临床研究。我们评估了短期和长期尼古丁戒断引起的斑马鱼行为和神经化学变化。斑马鱼暴露于1 mg/L尼古丁2周。使用行为分析确定依赖性后，美加明诱导的戒断，和脑烟碱受体结合研究。在2 - 60天自发戒断后，评估尼古丁暴露组和对照组鱼的焦虑样行为、快感缺乏和记忆缺陷。在最后一次药物暴露后7天和60天，使用尼古丁处理和对照鱼的全脑样品进行基因表达分析。还分析了前顶盖中酪氨酸羟化酶（TH）的免疫反应性。美加明沉淀戒断尼古丁暴露的鱼表现出增加焦虑样行为证明增加冻结和减少探索。尼古丁暴露2周后，~3H-表棘蛙素标记的异聚体烟碱乙酰胆碱受体（nAChR）显著增加，而~（125）I-α银环蛇毒素标记的同聚体nAChR无明显变化。自发尼古丁戒断引起焦虑样行为（底部停留增加），从戒断后第7天开始的位置偏好测试中对富集侧无偏好的动机降低，记忆注意力逐渐降低（辨别指数降低）。行为差异与脑基因表达变化相关：尼古丁戒断动物在60天后显示chrna 4和chrna 7表达降低，在7 - 60天显示htr 2a表达降低，c-Fos表达在7天显著增加。最后，酪氨酸羟化酶（TH）的免疫反应性增加，在背侧小细胞顶盖前核，但不是在室周核的后结节，也不在视顶盖，在60天后撤出。我们的研究结果表明，尼古丁戒断诱导焦虑样行为，认知改变，基因表达的变化和前顶盖TH表达的增加，类似于在人类和啮齿动物模型中观察到的。
Nicotine withdrawal syndrome is a major clinical problem. Animal models with sufficient predictive validity to support translation of pre-clinical findings to clinical research are lacking. We evaluated the behavioural and neurochemical alterations in zebrafish induced by short- and long-term nicotine withdrawal. Zebrafish were exposed to 1 mg/L nicotine for 2 weeks. Dependence was determined using behavioural analysis following mecamylamine-induced withdrawal, and brain nicotinic receptor binding studies. Separate groups of nicotine-exposed and control fish were assessed for anxiety-like behaviours, anhedonia and memory deficits following 2–60 days spontaneous withdrawal. Gene expression analysis using whole brain samples from nicotine-treated and control fish was performed at 7 and 60 days after the last drug exposure. Tyrosine hydroxylase (TH) immunoreactivity in pretectum was also analyzed. Mecamylamine-precipitated withdrawal nicotine-exposed fish showed increased anxiety-like behaviour as evidenced by increased freezing and decreased exploration. 3H-Epibatidine labeled heteromeric nicotinic acethylcholine receptors (nAChR) significantly increased after 2 weeks of nicotine exposure while 125I-αBungarotoxin labelled homomeric nAChR remained unchanged. Spontaneous nicotine withdrawal elicited anxiety-like behaviour (increased bottom dwelling), reduced motivation in terms of no preference for the enriched side in a place preference test starting from Day 7 after withdrawal and a progressive decrease of memory attention (lowering discrimination index). Behavioural differences were associated with brain gene expression changes: nicotine withdrawn animals showed decreased expression of chrna 4 and chrna7 after 60 days, and of htr2a from 7 to 60 days.The expression of c-Fos was significantly increased at 7 days. Finally, Tyrosine hydroxylase (TH) immunoreactivity increased in dorsal parvocellular pretectal nucleus, but not in periventricular nucleus of posterior tuberculum nor in optic tectum, at 60 days after withdrawal. Our findings show that nicotine withdrawal induced anxiety-like behaviour, cognitive alterations, gene expression changes and increase in pretectal TH expression, similar to those observed in humans and rodent models.
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影响因子：
4.2
作者：
Begh R;Munafò MR;Shiffman S;Ferguson SG;Nichols L;Mohammed MA;Holder RL;Sutton S;Aveyard P
通讯作者：
Aveyard P
影响因子：
3.4
作者：
Braida, Daniela;Ponzoni, Luisa;Sala, Mariaelvina
通讯作者：
Sala, Mariaelvina
影响因子：
4.6
作者：
Barbot A;Carrasco M
通讯作者：
Carrasco M
影响因子：
8.2
作者：
Hall FS;Der-Avakian A;Gould TJ;Markou A;Shoaib M;Young JW
通讯作者：
Young JW
α7和α4Beta2烟碱受体在斑点诱导的斑马鱼中的作用。
影响因子：
2.9
作者：
Bencan, Zachary;Levin, Edward D.
通讯作者：
Levin, Edward D.