Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
CNR Neuroscience Institute, Vedano al Lambro, MB, Italy.
J Psychopharmacol. 2023 Nov;37(11):1132-1148. doi: 10.1177/02698811231191103. Epub 2023 Aug 18.
Nicotine cessation leads to anxiety and depression.
The suitability of the zebrafish model of anhedonia using reserpine and fluoxetine was evaluated. Fluoxetine was also used to reduce nicotine withdrawal-induced anhedonic state.
Zebrafish were exposed to reserpine (40 mg/l) and then to fluoxetine (0.1 mg/l) for 1 week. Anhedonia was evaluated in the Novel Tank Diving and Compartment Preference tests. Another group was exposed to nicotine (1 mg/l/2 weeks) and then exposed to fluoxetine. Anxiety and anhedonia were evaluated 2-60 days after. Tyrosine hydroxylase (TH) immunoreactivity and microglial morphology (labelled by 4C4 monoclonal antibody) in the parvocellular pretectal nucleus (PPN), dorsal part, and of calcitonin gene-related peptide (CGRP) in the hypothalamus were also analysed.
Less time in the top and increased latency to the top in reserpine compared to a drug-free group was found. Fluoxetine rescued reserpine-induced the reduced time in the top. Seven and 30 days after nicotine withdrawal more time in the bottom and similar time in the Compartment Preference test, rescued by fluoxetine, were shown. In the PPN, 30-day withdrawal induced an increase in TH immunoreactivity, but fluoxetine induced a further significant increase. No changes in PPN microglia morphology and hypothalamic CGRP were detected.
Our findings validate the suitability of the zebrafish model of anhedonia using the reserpine-induced depression-like behaviour and the predictivity using fluoxetine. Fluoxetine rescued nicotine withdrawal-induced anhedonic state, opening the possibility to screen new drugs to alleviate anxiety and depression in smokers during abstinence.
尼古丁戒断会导致焦虑和抑郁。
评估利血平和氟西汀诱导斑马鱼快感缺失模型的适用性。还使用氟西汀来减少尼古丁戒断引起的快感缺失状态。
斑马鱼暴露于利血平（40mg/L）中，然后暴露于氟西汀（0.1mg/L）中 1 周。在新坦克潜水和隔间偏好测试中评估快感缺失。另一组暴露于尼古丁（1mg/L/2 周），然后暴露于氟西汀。在戒断后 2-60 天评估焦虑和快感缺失。还分析了下丘脑中小脑顶核（PPN）背侧部分的酪氨酸羟化酶（TH）免疫反应性和小胶质细胞形态（用 4C4 单克隆抗体标记）和降钙素基因相关肽（CGRP）。
与无药物组相比，利血平组在顶部的停留时间减少，到达顶部的潜伏期增加。氟西汀挽救了利血平引起的停留时间减少。在尼古丁戒断后 7 天和 30 天，显示出更多时间停留在底部，并且通过氟西汀挽救了在隔间偏好测试中的相似时间。在 PPN 中，30 天戒断引起 TH 免疫反应性增加，但氟西汀诱导进一步显著增加。未检测到 PPN 小胶质细胞形态和下丘脑 CGRP 的变化。
我们的发现验证了使用利血平诱导的抑郁样行为和使用氟西汀的预测性来建立斑马鱼快感缺失模型的适用性。氟西汀挽救了尼古丁戒断引起的快感缺失状态，为筛选新的药物以减轻戒烟期间吸烟者的焦虑和抑郁开辟了可能性。
