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急性多巴胺能和5-羟色胺能操作在ACI范式中的作用取决于大鼠认知判断偏差的基础效价。

Effects of acute dopaminergic and serotonergic manipulations in the ACI paradigm depend on the basal valence of cognitive judgement bias in rats.

作者信息

Golebiowska Joanna, Rygula Rafal

机构信息

Institute of Pharmacology Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, Affective Cognitive Neuroscience Laboratory, 12 Smetna Street, 31-343 Krakow, Poland.

Institute of Pharmacology Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, Affective Cognitive Neuroscience Laboratory, 12 Smetna Street, 31-343 Krakow, Poland.

出版信息

Behav Brain Res. 2017 Jun 1;327:133-143. doi: 10.1016/j.bbr.2017.02.013. Epub 2017 Feb 14.

Abstract

Recent findings have revealed that pharmacological enhancement of dopaminergic (DA) function by the administration of a DA precursor (dihydroxy-l-phenylalanine; L-DOPA), but not the selective serotonin reuptake inhibitor (SSRI) citalopram, increases an optimism bias in humans. To test whether dopamine might play a similar role in non-human animals, in the present study, we evaluated the effects of acute injections of L-DOPA, the D2 receptor antagonist haloperidol, and the SSRI escitalopram on cognitive judgement bias of rats in the ambiguous-cue interpretation (ACI) paradigm. Three different doses of each drug were administered in a fully randomised Latin-square design, along with saline treatment as a control, 30min before the ACI tests. Initial analysis revealed that only animals treated with L-DOPA were more 'pessimistic' than the saline-treated controls. Neither haloperidol nor escitalopram significantly affected the cognitive judgement bias of rats. However, further analysis revealed that the effects of the tested compounds might depend on the basal cognitive judgement bias of the tested animals. When we divided the rats into 'optimistic' and 'pessimistic' groups based on their cognitive judgement bias in the drug-free state, it turned out that acute administration of L-DOPA caused a 'pessimistic' shift in 'optimistic' animals while showing no significant effects on 'pessimists'. Acute administration of haloperidol caused a 'pessimistic' shift in 'optimistic' animals and an 'optimistic' shift in 'pessimists'. Acute administration of escitalopram caused a 'pessimistic' shift in 'optimistic' animals and had no significant effects on 'pessimists', except that the middle tested dose rendered the rats more 'optimistic'.

摘要

最近的研究发现,通过给予多巴胺前体(二羟基-L-苯丙氨酸;L-多巴)来增强多巴胺能(DA)功能,而非选择性5-羟色胺再摄取抑制剂(SSRI)西酞普兰,会增加人类的乐观偏差。为了测试多巴胺在非人类动物中是否可能发挥类似作用,在本研究中,我们评估了急性注射L-多巴、D2受体拮抗剂氟哌啶醇和SSRI艾司西酞普兰对大鼠在模糊线索解释(ACI)范式中的认知判断偏差的影响。每种药物的三种不同剂量以完全随机的拉丁方设计给药,同时给予生理盐水处理作为对照,在ACI测试前30分钟进行。初步分析显示,只有接受L-多巴治疗的动物比接受生理盐水处理的对照组更“悲观”。氟哌啶醇和艾司西酞普兰均未显著影响大鼠的认知判断偏差。然而,进一步分析显示,受试化合物的作用可能取决于受试动物的基础认知判断偏差。当我们根据大鼠在无药物状态下的认知判断偏差将其分为“乐观”和“悲观”两组时,结果发现急性给予L-多巴会使“乐观”动物出现“悲观”转变,而对“悲观”动物无显著影响。急性给予氟哌啶醇会使“乐观”动物出现“悲观”转变,使“悲观”动物出现“乐观”转变。急性给予艾司西酞普兰会使“乐观”动物出现“悲观”转变,对“悲观”动物无显著影响,只是中间测试剂量使大鼠更“乐观”。

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