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Age-related differences in anxiety-like behavior and amygdalar CCL2 responsiveness to stress following alcohol withdrawal in male Wistar rats

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Abstract

Rationale

Behavioral and neuroimmune vulnerability to withdrawal from chronic alcohol varies with age. The relation of anxiety-like behavior to amygdalar CCL2 responses following stress after withdrawal from chronic intermittent alcohol (CIA) was investigated in adolescent and adult rats.

Methods

Adolescent and adult Wistar rats were exposed to CIA (three 5-day blocks of dietary alcohol separated by 2 days of withdrawal) at concentrations that created similar blood alcohol levels across age. Twenty-four hours into the final withdrawal, half of the rats were exposed to 1 h of restraint stress. Four hours post-stress, rats were used for behavior or tissue assays.

Results

Anxiety-like behavior was increased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 mRNA was increased versus controls by CIA in adolescents and by CIA and CIA + stress in adults. CCL2 co-localization with neuronal marker NeuN was decreased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 co-localization with astrocytic marker GFAP was decreased versus controls by CIA and CIA + stress in adolescents, but experimental groups did not differ from controls in adults. CCL2 co-localization with microglial marker Iba1 was decreased versus controls by stress alone in adolescents and by CIA + stress in adults.

Conclusions

Changes in CCL2 protein might control behavior at either age but are particularly associated with CIA alone in adolescents and with CIA + stress in adults. That the number of CeA neurons expressing CCL2 was altered after CIA and stress is consistent with CCL2 involvement in neural function.

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Acknowledgments

We thank Faith Jeffers, Jenny Jin, and Edith Rivera for assistance with dietary procedures. We also thank Drs. Hugh Criswell and Jane Saiers for editorial assistance. This work was supported by Grants AA021275, AA007573, and AA011605 from the National Institute on Alcohol Abuse and Alcoholism.

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Authors and Affiliations

  1. Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, School of Medicine, CB#7178, 3006 Thurston-Bowles Building, Chapel Hill, NC, 27599-7178, USA

    Kathryn M Harper, Darin J Knapp, Meredith A. Park & George R Breese

  2. Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Darin J Knapp & George R Breese

  3. Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    George R Breese

  4. Curriculum in Neurobiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    George R Breese

  5. The UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    George R Breese

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  1. Kathryn M Harper
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  2. Darin J Knapp
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  3. Meredith A. Park
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  4. George R Breese
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Correspondence to Darin J Knapp.

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Harper, K.M., Knapp, D.J., Park, M.A. et al. Age-related differences in anxiety-like behavior and amygdalar CCL2 responsiveness to stress following alcohol withdrawal in male Wistar rats. Psychopharmacology 234, 79–88 (2017). https://doi.org/10.1007/s00213-016-4439-y

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  • DOI: https://doi.org/10.1007/s00213-016-4439-y

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