Aliphon Benjamin, Dai Twain, Moretti Jessica, Penrose-Menz Marissa, Mulders Wilhelmina H A M, Blache Dominique, Rodger Jennifer
School of Biological Sciences, University of Western Australia, Crawley, Australia.
School of Human Sciences, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
Psychopharmacology (Berl). 2023 Nov;240(11):2257-2270. doi: 10.1007/s00213-022-06281-8. Epub 2022 Dec 1.
There is an urgent need to identify behaviours in animals that can provide insight into the aetiology and potential treatment of depression in humans.
This study aimed to validate a repeated measures cognitive affective bias (CAB) test in a rat model of chronic stress and compare CAB with forced swim test (FST) measures.
Male and female Sprague Dawley rats were trained to associate large and small rewards with scent, spatial, and tactile cues, and their response to an ambiguous tactile stimulus tested. Rats underwent weekly CAB testing for 4 weeks with no intervention, or for 2 weeks of chronic restraint stress (CRS), followed by 2 weeks of fluoxetine, vehicle, or no treatment. CRS rats also underwent the FST at selected timepoints.
In control rats, CAB was positive and remained stable over the 4-week period. In CRS-fluoxetine and CRS-vehicle groups, CAB was initially positive, became negative during chronic restraint stress, and returned to positive by 2 weeks after treatment. However, in the CRS-no treatment group, CAB was variable at the outset and unstable over time. Behaviour in the FST was not affected by treatment, and there was no correlation between CAB and FST outcomes.
Instability in the CRS-no treatment group precluded interpretation of the impact of fluoxetine on CAB post-CRS. Our results suggest that behaviour in the FST does not reflect or alter affective state and support the use of CAB tests as part of the behavioural testing repertoire for preclinical animal models of affective disorders.
迫切需要确定动物的行为，以便深入了解人类抑郁症的病因和潜在治疗方法。
本研究旨在验证慢性应激大鼠模型中的重复测量认知情感偏差（CAB）测试，并将CAB与强迫游泳测试（FST）指标进行比较。
对雄性和雌性Sprague Dawley大鼠进行训练，使其将大小奖励与气味、空间和触觉线索联系起来，并测试它们对模糊触觉刺激的反应。大鼠每周进行一次CAB测试，持续4周，期间不进行干预，或进行2周的慢性束缚应激（CRS），随后进行2周的氟西汀、赋形剂或不治疗。CRS大鼠在选定的时间点也进行FST。
在对照大鼠中，CAB为阳性，且在4周内保持稳定。在CRS-氟西汀组和CRS-赋形剂组中，CAB最初为阳性，在慢性束缚应激期间变为阴性，并在治疗后2周恢复为阳性。然而，在CRS-不治疗组中，CAB一开始变化不定，且随时间不稳定。FST中的行为不受治疗影响，CAB与FST结果之间无相关性。
CRS-不治疗组的不稳定性使得无法解释氟西汀对CRS后CAB的影响。我们的结果表明，FST中的行为不能反映或改变情感状态，并支持将CAB测试作为情感障碍临床前动物模型行为测试方法的一部分。
