Abstract
Background
Adolescent alcohol exposure may increase depression vulnerability in adulthood by increasing the anhedonic response to stress.
Methods
Male Wistar rats (postnatal days 28–53) were exposed to binge-like adolescent intermittent ethanol (AIE) or water. In adulthood, rats were exposed to social defeat, consisting of daily confrontations with an aggressive conspecific, followed by testing of brain reward function in a discrete-trial current-intensity intracranial self-stimulation procedure for 10 consecutive days. Neurochemistry and corticotropin-releasing factor (CRF) and CRF receptor 1 (CRFR1) mRNA levels were assessed in corticolimbic brain areas on day 11 of social defeat stress.
Results
Social defeat elevated reward thresholds in both AIE- and water-exposed rats indicating stress-induced anhedonia. However, AIE-exposed rats were more likely to show threshold elevations after repeated stress compared to water-exposed rats. AIE exposure decreased CRF mRNA levels in the nucleus accumbens and increased CRFR1 mRNA levels in the prefrontal cortex, while stress increased CRF mRNA levels in the central amygdala. In the caudate putamen, AIE exposure decreased dopamine turnover, while stress increased glutamate and serotonin metabolism and turnover.
Conclusions
These results demonstrate increased risk of repeated stress-induced anhedonia after AIE exposure, an effect that may be due to alterations in brain CRF and dopamine systems. These results suggest that the increased rates of depression reported in people with a history of adolescent alcohol exposure may be related to alterations in brain reward and stress systems that may contribute to increased stress-induced anhedonia.
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Acknowledgments
This work was supported by NIH grant: U01-AA019970-NADIA (AM) and U01-AA019973-NADIA (SL). The NIH had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit the article for publication.
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Nathalie Boutros and Andre Der-Avakian are first co-authors
Athina Markou and Svetlana Semenova are senior co-authors
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Boutros, N., Der-Avakian, A., Kesby, J.P. et al. Effects of adolescent alcohol exposure on stress-induced reward deficits, brain CRF, monoamines and glutamate in adult rats. Psychopharmacology 235, 737–747 (2018). https://doi.org/10.1007/s00213-017-4789-0
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DOI: https://doi.org/10.1007/s00213-017-4789-0