Increased Response to 3,4-Methylenedioxymethamphetamine (MDMA) Reward and Altered Gene Expression in Zebrafish During Short- and Long-Term Nicotine Withdrawal.

Increased Response to 3,4-Methylenedioxymethamphetamine (MDMA) Reward and Altered Gene Expression in Zebrafish During Short- and Long-Term Nicotine Withdrawal.
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DOI:
10.1007/s12035-020-02225-5
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发表时间:
2021-04
影响因子:
5.1
通讯作者:
Sala M
Sala M
中科院分区:
医学2区
文献类型:
--
作者:
Ponzoni L;Teh MT;Torres-Perez JV;Brennan CH;Braida D;Sala M

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尼古丁和3,4-亚甲二氧基甲基苯丙胺(MDMA)之间的相互作用已被报道,但这种相互作用的机制尚未完全了解。这项研究使用斑马鱼探索与暴露于尼古丁2周和尼古丁戒断2-60天后对MDMA奖励效应敏感性改变相关的基因表达变化。使用条件性位置偏好(CPP)范式评估对MDMA的奖励反应,并使用药物处理和对照成年斑马鱼全脑样本mRNA的定量真实的时间PCR评价基因表达。与未暴露的鱼相比,在第2、7、30和60天停药时,预先暴露于尼古丁2周的斑马鱼对低剂量(0.1 mg/kg)MDMA的反应显示出条件性位置偏好增加。预暴露于尼古丁两周诱导c-Fos和加压素受体的表达显着增加,但D3多巴胺能和催产素受体的表达减少,在2天的撤退。C-Fos mRNA在停药后7、30、60 d也有增加。尼古丁预暴露的斑马鱼接受MDMA诱导的CPP,显示第2天p35、第30天α4、第7天加压素和第7、30和60天D3多巴胺能受体的表达增加。这些基因的改变可以解释尼古丁预暴露的鱼类对MDMA奖励效应的敏感性改变,这表明斑马鱼在尼古丁戒断期间调节行为作为奖励功能的能力改变。
An interactive effect between nicotine and 3,4 methylenedioxymethamphetamine (MDMA) has been reported but the mechanism underlying such interaction is not completely understood. This study used zebrafish to explore gene expression changes associated with altered sensitivity to the rewarding effects of MDMA following 2 week exposure to nicotine and 2-60 days of nicotine withdrawal. Reward responses to MDMA were assessed using a conditioned place preference (CPP) paradigm and gene expression was evaluated using quantitative real time PCR of mRNA from whole brain samples from drug-treated and control adult zebrafish. Zebrafish pre-exposed for 2 weeks to nicotine showed increased conditioned place preference in response to low dose, 0.1 mg/kg, MDMA compared to un-exposed fish at 2, 7, 30 and 60 days withdrawal. Pre-exposure to nicotine for two weeks induced a significant increase of c-Fos and vasopressin receptor expression but a decrease of D3 dopaminergic and oxytocin receptor expression at 2 days of withdrawal. C-Fos mRNA increased also at 7, 30, 60 days of withdrawal. Nicotine pre-exposed zebrafish submitted to MDMA-induced CPP, showed an increase in expression of p35 at day 2, α4 at day 30, vasopressin at day 7, and D3 dopaminergic receptor at day 7, 30, and 60. These gene alterations could account for the altered sensitivity to the rewarding effects of MDMA in nicotine pre-exposed fish, suggesting that zebrafish have an altered ability to modulate behaviour as a function of reward during nicotine withdrawal.
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