Unveiling the power of optimism: Exploring behavioral and neuromolecular correlates of alcohol seeking and drinking in rats with biased judgement

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2024-08-20 DOI:10.1016/j.pnpbp.2024.111124

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Abstract

Alcohol use disorder (AUD) is a common psychiatric condition with substantial global mortality. Despite extensive research into its pathophysiology, the cognitive predispositions driving alcohol dependence are less understood. This study explores whether biased cognition, specifically traits of optimism and pessimism, predicts susceptibility to alcohol-seeking behaviors using an animal model.

Rats were initially tested for judgement bias through Ambiguous Cue Interpretation tests. Those identified as ‘optimistic' or ‘pessimistic' were further examined for their tendency to escalate alcohol intake using the intermittent access 2-bottle choice (2BC) paradigm. Additionally, we assessed how judgement bias influenced the development of compulsive alcohol-seeking behavior in a Seeking-Taking (ST) and Seeking-Taking Punishment tasks, alcohol-seeking motivation in the Progressive Ratio Schedule of Reinforcement paradigm, the speed of extinction, and reinstatement after abstinence. Neurochemical analyses were conducted to investigate trait-specific differences in neurotransmitter-related gene expression and receptor densities in the brain. We used TaqMan Gene Expression Array Cards to analyze expression levels of genes linked to serotonergic, dopaminergic, glutamatergic, and GABAergic pathways, and alcohol metabolism in various brain regions. Receptor densities for 5-HT_1A, 5-HT_2A, and D₂ were measured using autoradiography analysis.

Behaviorally, ‘optimistic' rats showed significantly lower alcohol consumption in the 2BC paradigm compared to ‘pessimistic' rats. This lowered intake correlated with decreased monoamine oxidase-A (Maoa) expression in the medial prefrontal cortex (mPFC) and increased metabotropic glutamate receptor 2 (Grm2) expression in the amygdala (Amy). Additionally, we observed significant interactions between judgement bias and alcohol intake in the expression of several genes in the mPFC, nucleus accumbens (Nacc), orbitofrontal cortex (OFC), and Amy, as well as in 5-HT_2A receptor binding in the Nacc.

Overall, these results suggest that optimism is linked to lower alcohol consumption and related neurochemical changes, indicating a potential cognitive mechanism in AUD risk.

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揭示乐观的力量：探索具有偏差判断力的大鼠寻求酒精和饮酒的行为和神经分子相关性。

酒精使用障碍（AUD）是一种常见的精神疾病，全球死亡率很高。尽管对其病理生理学进行了广泛的研究，但人们对导致酒精依赖的认知倾向却不甚了解。本研究利用动物模型探讨了偏差认知（特别是乐观和悲观的特征）是否能预测酗酒行为的易感性。首先通过模糊线索解释测试对大鼠进行判断偏差测试。对那些被认定为 "乐观 "或 "悲观 "的大鼠，我们采用间歇性双瓶选择（2 BCE）范式进一步检测了它们酒精摄入量增加的倾向。此外，我们还评估了判断偏差如何影响 "寻求-摄取（ST）"和 "寻求-摄取惩罚（ST）"任务中强迫性觅酒行为的发展、"渐进比率强化表（Progressive Ratio Schedule of Reinforcement）"范式中的觅酒动机、消退速度以及戒酒后的恢复。我们进行了神经化学分析，以研究大脑中神经递质相关基因表达和受体密度的特异性差异。我们使用 TaqMan 基因表达阵列卡分析了与血清素能、多巴胺能、谷氨酸能和 GABA 能通路以及酒精代谢有关的基因在不同脑区的表达水平。通过自显影分析测量了 5-HT1A、5-HT2A 和 D2 的受体密度。在行为上，与 "悲观 "大鼠相比，"乐观 "大鼠在 2 BCE 范式中的酒精摄入量明显较低。摄入量的降低与内侧前额叶皮层（mPFC）中单胺氧化酶-A（Maoa）表达的减少和杏仁核（Amy）中代谢型谷氨酸受体 2（Grm2）表达的增加有关。此外，我们还观察到判断偏差与酒精摄入量之间在 mPFC、伏隔核 (Nacc)、眶额皮层 (OFC) 和艾米中几个基因的表达，以及在伏隔核中 5-HT2A 受体结合方面的显著交互作用。总之，这些结果表明，乐观情绪与较低的酒精消耗量和相关神经化学变化有关，这表明了潜在的认知机制对 AUD 风险的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Progress in Neuro-Psychopharmacology & Biological Psychiatry 医学-精神病学

CiteScore

12.00

自引率

1.80%

发文量

153

审稿时长

56 days

期刊介绍： Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.