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

Author(s)

Conto, Marcos Brandao ^[1] ; dos Santos, Nilton Barreto ^[1] ; Munhoz, Carolina Demarchi ^[1] ; Marcourakis, Tania ^[2] ; D'Almeida, Vania ^[3] ; Camarini, Rosana ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Cioncias Biomed, Dept Farmacol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Psicobiol, Escola Paulista Med UNIFESP EPM, Sao Paulo - Brazil

• Document type: Journal article
• Source: Neuroscience; v. 469, p. 125-137, AUG 10 2021.
• Web of Science Citations: 0

Abstract

Alchohol 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 SIRT2 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 EthanolSedentary group. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 18/05038-0 - Effect of environmental enrichment on resilience to chronic unpredictable stress: epigenetic regulation of the BDNF gene and consequences on ethanol consumption
• Grantee: Rosana Camarini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/09898-7 - Effects of different forms of environmental stimulation on the alcohol-induced behavioral alterations: Involvement of epigenetic modifications and of transcriptional and neurotrophic factors
• Grantee: Marcos Brandão Contó
• Support Opportunities: Scholarships in Brazil - Post-Doctoral