Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, England, UK.
Mol Neurobiol. 2021 Apr;58(4):1650-1663. doi: 10.1007/s12035-020-02225-5. Epub 2020 Nov 24.
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 2 weeks induced a significant increase of c-Fos and vasopressin receptor expression but a decrease of D 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 D 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.
已经报道了尼古丁和 3,4-亚甲基二氧甲基苯丙胺（MDMA）之间的相互作用，但这种相互作用的机制尚不完全清楚。本研究使用斑马鱼来探索与尼古丁暴露 2 周后对 MDMA 的奖赏效应敏感性改变相关的基因表达变化，以及尼古丁戒断 2-60 天后的基因表达变化。使用条件性位置偏爱（CPP）范式评估 MDMA 的奖赏反应，并用经药物处理和对照成年斑马鱼的全脑样本的实时定量 PCR 评估基因表达。与未暴露的鱼相比，暴露于尼古丁 2 周的斑马鱼在 2、7、30 和 60 天戒断时对低剂量（0.1 mg/kg）MDMA 表现出增强的条件性位置偏好。尼古丁暴露 2 周诱导了 c-Fos 和加压素受体表达的显著增加，但在戒断 2 天时 dopaminergic 和催产素受体表达减少。c-Fos mRNA 也在戒断 7、30 和 60 天增加。在接受 MDMA 诱导的 CPP 的尼古丁暴露斑马鱼中，p35 在第 2 天、α4 在第 30 天、加压素在第 7 天和 dopaminergic 受体在第 7、30 和 60 天表达增加。这些基因改变可能解释了尼古丁暴露的鱼对 MDMA 的奖赏效应敏感性改变，表明在尼古丁戒断期间，斑马鱼改变了调节行为以适应奖赏的能力。
