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Exposure to Running Wheels Prevents Ethanol Rewarding Effects: The Role of CREB and Deacetylases SIRT-1 and SIRT-2 in the Nucleus Accumbens and Prefrontal Cortex.
- Source :
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Neuroscience [Neuroscience] 2021 Aug 10; Vol. 469, pp. 125-137. Date of Electronic Publication: 2021 Jun 24. - Publication Year :
- 2021
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Abstract
- Alcohol use disorder is one of the most prevalent addictions, strongly influenced by environmental factors. Voluntary physical activity (VPA) has proven to be intrinsically reinforcing and we hypothesized that, as a non-drug reinforcer, VPA could mitigate ethanol-induced rewarding effects. The transcriptional factor cAMP response element binding protein (CREB), and deacetylases isozymes sirtuins 1 and 2 (SIRT-1 and SIRT-2) have a complex interplay and both play a role in the rewarding effects of ethanol. To test whether the exposure of mice to running wheels inhibits the development of ethanol-induced conditioned place preference (CPP), mice were assigned into four groups: housed in home cages with locked ("Sedentary") or unlocked running wheels (VPA), and treated with saline or 1.8 g/kg ethanol during the conditioning phase. The groups were referred as Saline-Sedentary, Saline-VPA, Ethanol-Sedentary and Ethanol-VPA. The expression of CREB, SIRT-1 and SIRT-2 were evaluated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). VPA prevented the development of ethanol-induced CPP. VPA, ethanol and the combination of both inhibited pCREB and pCREB/CREB ratio in the NAc, suggesting that both reward stimuli can share similar patterns of CREB activation. However, we have found that ethanol-induced increased CREB levels were prevented by VPA. Both VPA groups presented lower SIRT-1 levels in the NAc compared to the Sedentary groups. Thus, exposure to running wheels prevented ethanol-rewarding effects and ethanol-induced increases in CREB in the NAc. The molecular alterations underlying CPP prevention may be related to a lower expression of CREB in the NAc of Ethanol-VPA compared to the respective Sedentary group, given the positive correlation between CPP and CREB levels in the Ethanol-Sedentary group.<br />Competing Interests: Conflict of interest The authors declare that they have no competing interest.<br /> (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 469
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 34175423
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2021.06.029