Fureix Carole, Trevarthen Anna C, Finnegan Emily M, Bučková Katarína, Paul Elizabeth S, Mendl Michael T
University of Bristol, Bristol Veterinary School, Langford House, Langford BS40 5DU, United Kingdom.
University of Bristol, Bristol Veterinary School, Langford House, Langford BS40 5DU, United Kingdom.
Pharmacol Biochem Behav. 2022 Jan;212:173311. doi: 10.1016/j.pbb.2021.173311. Epub 2021 Dec 1.
We previously identified in laboratory mice an inactive state [being awake with eyes open motionless within the home cage; inactive but awake, 'IBA'] sharing etiological factors and symptoms with human clinical depression. We further test the hypothesis that greater time spent displaying IBA indicates a depression-like state in mice by investigating whether the antidepressant Venlafaxine, environmental enrichment, and their combination, alleviate IBA. Seventy-two C57BL/6J and 72 DBA/2J female mice were pseudo-randomly housed post-weaning in mixed strain-pairs in non-enriched (NE; 48 pairs) or in environmentally enriched (EE; 24 pairs) cages. After 34 days, half of the mice housed in NE cages were either relocated to EE cages or left in NE cages. For each of these conditions, half of the mice drank either a placebo or the antidepressant Venlafaxine (10 mg/kg). The 48 mice housed in EE cages were all relocated to NE cages and allocated to either the placebo (n = 24) or Venlafaxine (n = 24). IBA data were collected prior to and after environmental adjustment by trained observers blind to the pharmacological and environmental adjustment treatments. Data were analyzed using GLM models. NE cages triggered more IBA than EE cages (Likelihood-Ratio-Test Chi = 53.501, p < 0.0001). Venlafaxine and environmental enrichment appeared equally effective at reducing IBA (LRT Chi = 18.262, p < 0.001), and combining these approaches did not magnify their effects. Enrichment removal triggered IBA increase (LRT Chi = 23.050, p < 0.001), but Venlafaxine did not overcome the increase in IBA resulting from enrichment loss (LTR Chi = 0.081, p = 0.775). Theoretical implications for putative depression-like states in mice, and further research directions, are discussed.
我们之前在实验小鼠中发现了一种无活动状态[在饲养笼内睁着眼睛静止不动；无活动但清醒，即“清醒无活动状态（IBA）”]，它与人类临床抑郁症有着共同的病因和症状。我们进一步检验了这样一个假设：通过研究抗抑郁药文拉法辛、环境丰富化及其组合是否能减轻清醒无活动状态，来确定在小鼠中，处于清醒无活动状态的时间越长是否表明其处于类似抑郁的状态。72只C57BL/6J和72只DBA/2J雌性小鼠在断奶后以混合品系对的形式伪随机饲养在未富集（NE；48对）或环境富集（EE；24对）的笼子中。34天后，饲养在NE笼子中的一半小鼠要么被转移到EE笼子中，要么留在NE笼子中。对于这些条件中的每一种，一半的小鼠饮用安慰剂或抗抑郁药文拉法辛（10毫克/千克）。饲养在EE笼子中的48只小鼠全部被转移到NE笼子中，并被分配到安慰剂组（n = 24）或文拉法辛组（n = 24）。由对药理学和环境调整处理不知情的训练有素的观察者在环境调整前后收集清醒无活动状态的数据。使用广义线性模型（GLM）对数据进行分析。NE笼子引发的清醒无活动状态比EE笼子更多（似然比检验卡方值 = 53.501，p < 0.0001）。文拉法辛和环境丰富化在减少清醒无活动状态方面似乎同样有效（似然比检验卡方值 = 18.262，p < 0.001），并且将这些方法结合起来并没有增强它们的效果。去除丰富化环境引发了清醒无活动状态增加（似然比检验卡方值 = 23.050，p < 0.001），但文拉法辛并没有克服因丰富化环境丧失而导致的清醒无活动状态增加（似然比检验卡方值 = 0.081，p = 0.775）。文中讨论了对小鼠假定的类似抑郁状态的理论意义以及进一步的研究方向。
