Exploratory drive, fear, and anxiety are dissociable

Anxiety-like behavior of rodents is frequently accompanied by reduced exploration. Here, we identify dissociable components of anxiety, fear, and exploratory drive of sated and foraging mice. With the help of behavioral assays, including the open field task, elevated plus maze, dark–light transition task, and beetle mania task, we demonstrate a general increase in exploration by food restriction. Food-restricted mice bred for high anxiety behavior (HAB) showed ameliorated anxiety- but not fear-related behavior.

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FIG:Food restriction procedure and open field test (OFT): a HAB and NAB mice were either food restricted (FR+) to reach 85% (shaded area) of their original body weight (baseline, B) or continued to be fed ad libitum (FR−). The body weight remained fairly stable throughout the entire test battery comprised by open field test (OFT), elevated plus maze test (EPM), dark–light transition task (DaLi), and beetle mania test (BMT), with at least 7 days of recovery between two subsequent tasks. Numbers in brackets: sample sizes. b–fBehavioral performance during a 15-min exposure to the OFT. Mean ± SEM with individual data. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 (two-way ANOVA followed by Tukey’s post hoc test); in c, data points without shared letters are statistically significantly different (p < 0.05; three-way ANOVA for repeated measures, followed by Tukey’s post hoc test).

By means of principal component analysis, we identified three independent components, which resemble the behavioral dimensions proposed by Gray’s Reinforcement Sensitivity Theory (approach behavior, avoidance behavior, and decision making). Taken together, we demonstrate anxiolytic consequences of food restriction in a mouse model of anxiety disorders that can be dissociated from a general increase in foraging behavior.

Heinz, D.E., Schöttle, V.A., Nemcova, P. et al. Exploratory drive, fear, and anxiety are dissociable and independent components in foraging mice. Transl Psychiatry 11, 318 (2021). https://doi.org/10.1038/s41398-021-01458-9

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