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Making "Good" Choices: Social Isolation in Mice Exacerbates the Effects of Chronic Stress on Decision Making.

ABSTRACT: Chronic stress can impact decision-making and lead to a preference for immediate rewards rather than long-term payoffs. Factors that may influence these effects of chronic stress on decision-making are under-explored. Here we used a mouse model to investigate the changes in decision-making caused by the experience of chronic stress and the role of social isolation in exaggerating these changes. To test decision-making, mice were trained to perform a Cost-Benefit Conflict (CBC) task on a T-maze, in which they could choose between a high-reward, high-risk alternative and a low-reward, low-risk alternative. Mice were either housed in groups or alone throughout the experiment. Both groups of mice underwent a seven-day period of repeated immobilization to induce chronic stress. Stress levels were confirmed using behavioral (open field test) and physiological (urine corticosterone ELISA) measures. We found a significant increase in frequency of high-risk decisions after exposure to chronic stress among both socially- and individually-housed mice. Crucially, socially-housed mice showed a significantly smaller increase in high-risk decision-making compared to singly-housed mice. These findings suggest that chronic stress leads to an increase in high-risk decision-making in mice, and that lack of social interaction may exacerbate this stress effect.

SUBMITTER: Mudra Rakshasa A

PROVIDER: S-EPMC7261864 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Making "Good" Choices: Social Isolation in Mice Exacerbates the Effects of Chronic Stress on Decision Making.

Mudra Rakshasa Arish A Tong Michelle T MT

Frontiers in behavioral neuroscience 20200525

Chronic stress can impact decision-making and lead to a preference for immediate rewards rather than long-term payoffs. Factors that may influence these effects of chronic stress on decision-making are under-explored. Here we used a mouse model to investigate the changes in decision-making caused by the experience of chronic stress and the role of social isolation in exaggerating these changes. To test decision-making, mice were trained to perform a Cost-Benefit Conflict (CBC) task on a T-maze, ...[more]

PMID: 32523519

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Project description:Introduction: Smartphone Addiction (SA) has caused negative consequences and functional impairments in college students, such as reduction of academic performance and impairment in sleep quality. Studies have shown that individuals with chemical and behavioral dependencies have a bias in decision-making process, which leads to short-term advantageous choices even if they cause long-term harm. This bias in decision-making process is accompanied by a change in somatic markers and is associated with the development and maintenance of addictive behavior. The decision-making process and the measurement of physiological parameters have not yet been analyzed in SA. The neuropsychological and physiological characterization of the SA can contribute to its approach with the other dependency syndromes and to its recognition as a disease. Objective: we aimed to evaluate the decision-making process under risk and under ambiguity in individuals with SA and to measure the physiological parameters that accompany this process. Method: We compared the performance in the Iowa Gambling Task (IGT), Game of Dice Task (GDT) and skin conductance response (SCR) between 50 individuals with SA and 50 controls. Results: Smartphone dependents presented a profile of impairment in decision-making under ambiguity, without impairment in decision-making under risk. They demonstrated lower SCR before disadvantageous choices, higher SCR after rewards and lower SCR after punishments during decision-making, which suggests difficulty in recognizing disadvantageous alternatives, high sensitivity to rewards, and low sensitivity to punishments. Conclusion: The impairment in the decision-making process in smartphone dependents is similar to that found in other chemical and behavioral addictions, such as alcohol addiction, gambling disorders and pathological buy. The impairment in decision under ambiguity with preservation of decision under risk may reflect dysfunction of implicit emotional processes without dysfunction of explicit cognitive process. This profile can contribute to the recognition of SA as a behavioral dependence and to guide specific preventive and therapeutic strategies.

Project description:BackgroundOur previous studies indicated that N-methyl-D-aspartate receptor (NMDAR) deletion from a subset of corticolimbic interneurons in the mouse brain during early postnatal development is sufficient to trigger several behavioral and pathophysiological features resembling the symptoms of human schizophrenia. Interestingly, many of these behavioral phenotypes are exacerbated by social isolation stress. However, the mechanisms underlying the exacerbating effects of social isolation are unclear.MethodsWith γ-aminobutyric acid-ergic interneuron-specific NMDAR hypofunction mouse model (Ppp1r2-Cre/fGluN1 knockout [KO] mice), we investigated whether oxidative stress is implicated in the social isolation-induced exacerbation of schizophrenia-like phenotypes and further explored the underlying mechanism of elevated oxidative stress in KO mice.ResultsThe reactive oxygen species (ROS) level in the cortex of group-housed KO mice was normal at 8 weeks although increased at 16 weeks old. Postweaning social isolation (PWSI) augmented the ROS levels in KO mice at both ages, which was accompanied by the onset of behavioral phenotype. Chronic treatment with apocynin, an ROS scavenger, abolished markers of oxidative stress and partially alleviated schizophrenia-like behavioral phenotypes in KO mice. Markers of oxidative stress after PWSI were especially prominent in cortical parvalbumin (PV)-positive interneurons. The vulnerability of PV interneurons to oxidative stress was associated with downregulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a master regulator of mitochondrial energy metabolism and antioxidation.ConclusionsThese results suggest that a PWSI-mediated impairment in antioxidant defense mechanisms, presumably mediated by PGC-1α downregulation in the NMDAR-deleted PV-positive interneurons, results in oxidative stress, which, in turn, might contribute to exacerbation of schizophrenia-like behavioral phenotypes.

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Making "Good" Choices: Social Isolation in Mice Exacerbates the Effects of Chronic Stress on Decision Making.

Publications

Making "Good" Choices: Social Isolation in Mice Exacerbates the Effects of Chronic Stress on Decision Making.

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