Rapid-acting antidepressant drugs modulate affective bias in rats.
Rapid-acting antidepressant drugs modulate affective bias in rats.
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DOI：
10.1126/scitranslmed.adi2403
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发表时间：
2024-01-10
影响因子：
17.1
通讯作者：
Robinson ESJ
中科院分区：
文献类型：
--
作者：
Hinchcliffe JK;Stuart SA;Wood CM;Bartlett J;Kamenish K;Arban R;Thomas CW;Selimbeyoglu A;Hurley S;Hengerer B;Gilmour G;Robinson ESJ
速效抗抑郁药（RAAD），如氯胺酮，如何诱导重度抑郁症（MDD）患者情绪的立即和持续改善，目前尚不清楚。抑郁症的一个核心特征是与负性情感状态相关的认知加工偏差的普遍存在，负性情感偏差的减轻可能是药物治疗反应的指标。在这里，我们使用了一个情感偏见行为测试大鼠，基于联想学习任务，研究RAAD的影响。为了产生情感偏差，动物学会了在存在或不存在情感状态操纵的情况下将两种不同的挖掘基质与食物奖励联系起来。两个奖励相关的挖掘基板之间的选择被用来量化产生的情感偏见。急性治疗RAAD氯胺酮，东莨菪碱或裸盖菇素选择性地减弱了负的情感偏见的情感偏见测试。低剂量（但不是高剂量）氯胺酮和裸盖菇素逆转了RAAD治疗后24小时的负性情感偏差的效价。只有裸盖菇素，而不是氯胺酮或东莨菪碱，导致一个积极的情感偏见，这是依赖于新的学习和记忆的形成。氯胺酮的再学习效应依赖于定位于大鼠内侧前额叶皮质的蛋白质合成，并可通过线索再激活进行调制，这与经验依赖性神经可塑性一致。这些研究结果表明，一种神经心理学机制，可以解释急性和持续的影响RAAD，潜在地连接其对神经可塑性的影响与情感偏见调制在啮齿动物模型。
How rapid-acting antidepressants (RAADs), such as ketamine, induce immediate and sustained improvements in mood in patients with major depressive disorder (MDD) is poorly understood. A core feature of MDD is the prevalence of cognitive processing biases associated with negative affective states, and the alleviation of negative affective biases may be an index of response to drug treatment. Here, we used an affective bias behavioral test in rats, based on an associative learning task, to investigate the effects of RAADs. To generate an affective bias, animals learned to associate two different digging substrates with a food reward in the presence or absence of an affective state manipulation. A choice between the two reward-associated digging substrates was used to quantify the affective bias generated. Acute treatment with the RAADs ketamine, scopolamine or psilocybin selectively attenuated a negative affective bias in the affective bias test. Low, but not high, doses of ketamine and psilocybin reversed the valence of the negative affective bias 24 hours after RAAD treatment. Only psilocybin, but not ketamine or scopolamine, led to a positive affective bias that was dependent on new learning and memory formation. The re-learning effects of ketamine were dependent on protein synthesis localised to the rat medial prefrontal cortex and could be modulated by cue-reactivation, consistent with experience-dependent neural plasticity. These findings suggest a neuropsychological mechanism that may explain both the acute and sustained effects of RAADs, potentially linking their effects on neural plasticity with affective bias modulation in a rodent model.
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影响因子：
11
作者：
Chowdhury GM;Zhang J;Thomas M;Banasr M;Ma X;Pittman B;Bristow L;Schaeffer E;Duman RS;Rothman DL;Behar KL;Sanacora G
通讯作者：
Sanacora G
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
3.4
作者：
Hinchcliffe JK;Stuart SA;Mendl M;Robinson ESJ
通讯作者：
Robinson ESJ
影响因子：
4.8
作者：
Joormann, Jutta;Vanderlind, W. Michael
通讯作者：
Vanderlind, W. Michael
影响因子：
158.5
作者：
Goodwin, Guy M.;Aaronson, Scott T.;Malievskaia, Ekaterina
通讯作者：
Malievskaia, Ekaterina