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Séminaire impromptu - Ursula SkupioAstrocytic glucocorticoid receptor modulates opioid reward sensitivity

Abstract :

 Majority of research on involvement of glucocorticoids in addictive behaviors thus far was focused on neurons. Although it is recognized that astrocytes can control synaptic plasticity and express glucocorticoid receptor (GR), the potential role of astrocytic GR in the central actions mediated by glucocorticoids is largely unexplored. I would like to present some insight into the functional contribution of astrocytic GR to striatal reward circuity.

Our results show that GR-dependent transcriptional changes in astrocytes are a major site of glucocorticoids action in the brain. We have therefore silenced astrocytic GRs, using viral-mediated RNA interference in the nucleus accumbens in vivo. GR knockdown in astrocytes resulted in specific increase of sensitivity to opioid reward as well as alterations of morphine-induced synaptic plasticity. Thus, our results show notable contribution of astrocytes to long-recognized involvement of GR in addiction-like behaviors.

Selected publications

Behavioral and transcriptional patterns of protracted opioid self-administration in mice. Skupio U, Sikora M, Korostynski M, Wawrzczak-Bargiela A, Piechota M, Ficek J, Przewlocki R. Addict Biol. 2017 Nov;22(6):1802-1816. doi: 10.1111/adb.12449. Epub 2016 Aug 31. PMID: 27578564

Behavioral and molecular alterations in mice resulting from chronic treatment with dexamethasone: relevance to depression. Skupio U, Tertil M, Sikora M, Golda S, Wawrzczak-Bargiela A, Przewlocki R. Neuroscience. 2015 Feb 12;286:141-50. doi: 10.1016/j.neuroscience.2014.11.035. Epub 2014 Nov 27. PMID: 25433240

Scientific focus :

Our research focuses on neuronal mechanisms underlying the activity of the brain’s reward system. We investigate how plasticity in the reward system controls reinforcement learning and how the systems adapts to stress or the effects of drugs of abuse. Additionally, a considerable part of our research involves analysis of gene expression induced by psychoactive substances in the brain structures associated with the reward system. We hope that elucidating molecular signatures of drug action will lead to identification of mechanisms essential for their therapeutic effects...read more