An Olfactory Preference Test for Measuring Olfactory Hedonic Biases in Mouse Models of Depression

Claire-H&#233;l&#232;ne de Badts; Gilles Gheusi; Chantal Henry; Pierre-Marie Lledo; Mariana Alonso

doi:10.3791/68391

JoVE Journal
Neuroscience

This content is Free Access.

JoVE Journal Neuroscience

An Olfactory Preference Test for Measuring Olfactory Hedonic Biases in Mouse Models of Depression

测量抑郁症小鼠模型中嗅觉享乐偏差的嗅觉偏好测试

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06:27 min

July 11, 2025

DOI: 10.3791/68391-v

Claire-Hélène de Badts^1,2, Gilles Gheusi^1,3, Chantal Henry^1,4,5, Pierre-Marie Lledo¹, Mariana Alonso¹

¹Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3571,Institut Pasteur, Université Paris Cité, ²Ecole Doctorale 158 - Cerveau, Cognition, Comportement,Université Paris Cité, ³Laboratoire d’Ethologie Expérimentale et Comparée – UR 4443,Université Sorbonne Paris Nord, ⁴Université de Paris Cité, ⁵Department of Psychiatry, Service Hospitalo-Universitaire,GHU Paris Psychiatrie & Neuroscience

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Overview

This study presents a protocol for an olfactory preference test to evaluate negative olfactory biases towards both appetitive and aversive odor stimuli in mouse models of depression. Understanding these biases is crucial for investigating the physiopathology of depressive disorders and can aid in elucidating the underlying neural mechanisms and treatment outcomes.

Key Study Components

Area of Science

Neuroscience
Behavioral Analysis
Psychiatric Disorders

Background

Negative bias in emotional processing is prevalent in depressive disorders.
The assessment of innate odor valuation can help evaluate depressive-like phenotypes.
Research aims to explore neural circuits disrupted by depression.
Future work may include examining sex-specific mechanisms and antidepressant effects.

Purpose of Study

To develop a reliable method for assessing hedonic bias in mice.
To relate behavioral outcomes to neural mechanisms in depression.
To explore translational research avenues for understanding depression.

Methods Used

A two-compartment arena measuring 45 cm x 50 cm x 25 cm.
Mice were divided into control and experimental groups exposed to various odor stimuli.
Important steps included odor preparation, behavioral observation, and data tracking.
Mouse behavior was recorded for ten minutes to analyze preference and exploration.

Main Results

Control females showed greater movement in response to male urine than UCMS females.
UCMS mice exhibited reduced preference for odors associated with negative valence.
Behavioral indices positively correlated with emotionality scores in females.
In male mice, no significant differences in behavior were noted, highlighting sex-specific responses.

Conclusions

The protocol allows effective assessment of odor preference linked to depressive phenotypes.
Findings support insights into behavioral changes associated with depression and potential treatment efficacy.
This approach enhances understanding of mechanisms underlying emotional processing in depressive disorders.

Frequently Asked Questions

What are the advantages of using the olfactory preference test?

This test reliably assesses the innate value of odors and their emotional connotations in mouse models, providing insights into depressive behaviors.

How is the experimental setup prepared for the olfactory test?

A two-compartment arena is set up with odor stimuli placed on filter paper within Petri dishes. Mice are introduced into the center for observation.

What data is collected during the experiment?

Behavioral data including time spent in odor zones and exploration patterns are recorded. Automatic tracking software aids in analysis.

What types of odor stimuli are used in the assessment?

The study employs odors related to negative and positive emotional valence, specifically using stimuli such as male urine and TMT.

How can the methodology be adapted for further studies?

Future adaptations may include varying the types of odors or modifying the experimental conditions to assess different behavioral responses.

Are there any limitations to this olfactory preference test?

Potential limitations include the variability in individual mouse responses and the need for careful odor preparation to ensure consistency.

在这里，我们提出了一种嗅觉偏好测试的方案，该方案允许在抑郁症小鼠模型中评估对食欲和厌恶气味刺激的负面嗅觉偏差。

情绪处理中的负面偏见是抑郁症的一个主要特征。这种偏见对于更好地了解疾病的生理病理学特别有趣。在这里，我们提出了一种协议，用于使用与雄性和雌性抑郁症小鼠模型中各种化合价相关的气味来可靠评估先天气味评估。

评估小鼠模型中的享乐偏差至关重要，这既可以更好地评估诱导的抑郁样表型，也可以作为研究这些效价分配变化背后的神经机制的工具。总体而言，该协议为转化研究提供了新的途径，以了解抑郁症的潜在机制和治疗效果。未来，我们将尝试破译这些被破坏的情绪处理背后的大脑回路和潜在的性别特异性机制，以及抗抑郁药对这些途径的作用。

首先，使用尺寸为 45 厘米 x 50 厘米 x 25 厘米的两隔间竞技场准备实验装置，该竞技场具有灰色有机玻璃墙和白色地板。使用尺寸为 37 厘米 x 25 厘米的灰色有机玻璃墙，将竞技场分成两个相等的 25 厘米 x 45 厘米隔间。用粘合剂固定穿孔培养皿，并将它们放在每个隔间的墙底。

然后使用双面粘合剂或 Blu Tack 将每个培养皿垂直固定在竞技场的墙壁上。接下来，在竞技场上方两米处放置一个摄像头，以记录动物的行为，并在整个实验过程中自动跟踪它们的运动。现在将小鼠分为至少两个实验组，对照组小鼠和测试组小鼠。

在实验开始前 30 分钟将每只小鼠转移到行为测试室。使用照度计将竞技场内的照明设置为大约 40 勒克斯，并验证照明是否均匀分布。接下来，在竞技场中的两个培养皿中各添加一张 42.5 毫米的干净滤纸。

第一天，将同一笼子中的所有小鼠轻轻地放入竞技场中10分钟，以减少新恐惧症。在测试当天，使用正确的稀释液在玻璃瓶中准备化学罩下的气味。根据其化学性质在矿物油或蒸馏水中稀释气味剂。

在测试每只小鼠之前，使用带有过滤尖端的微型移液器在引擎盖下收集 200 微升气味溶液。将溶液分配到其中一个培养皿中的滤纸上。将另一个培养皿中的第二张滤纸留在不处理的情况下。

将培养皿转移到测试室。然后将它们垂直固定在竞技场的墙上。将每只鼠标单独放入两个隔间之间中央的竞技场中。

使用高架摄像头记录行为 10 分钟。观察期结束后将鼠标从竞技场中移开。从竞技场上去除气味培养皿。

然后使用 70% 乙醇消毒液清洁竞技场并彻底干燥。丢弃用过的滤纸，并为下一只小鼠准备下一个气味样本。使用自动跟踪软件在整个测试过程中记录鼠标的位置。

在竞技场内定义不同的区域以进行分析。在习惯化期间，所有小鼠在气味和控制区都至少花费了 50 秒，表明有足够的任务参与。重要的是，暴露于 UCMS 的小鼠在气味区花费的时间与对照组相同。

尽管在其他区域可以观察到一些差异。当暴露于雄性尿液时，对照雌性小鼠的移动量明显高于UCMS雌性，但在习惯化或TMT暴露期间则没有。所有享乐反应读数都显示对照组和 UCMS 女性之间存在显着差异或统计趋势。

这种影响也可以通过全球气味探索指数看到，该指数是享乐和运动反应的综合衡量标准。气味探索指数与雌性小鼠雄性尿液和TMT的情绪评分呈正相关。在雄性小鼠中，在习惯化过程中或通过测试移动的总距离上没有观察到差异。

与对照组相比，在气味区花费的时间表明 UCMS 中女性尿液和 TMT 探索显着减少。UCMS 小鼠进入气味区明显较少，或倾向于进入气味区，并且对雌性尿液和 TMT 的偏好指数显着降低。与对照组相比，气味探索指数显示 UCMS 小鼠对雌性尿液和 TMT 的行为反应呈负向偏移，这往往与动物的情绪评分呈正相关。