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. (10th August 2021)

• Record Type: Journal Article
• Authors: Contó, Marcos Brandão; dos Santos, Nilton Barreto; Munhoz, Carolina Demarchi; Marcourakis, Tania; D'Almeida, Vânia; Camarini, Rosana
• Is Part Of: Neuroscience. Volume 469(2021)
• Page Start: 125
• Page End: 137
• Publication Date: 2021-08-10
• Subjects: AUD alcohol use disorder -- CPP conditioned place preference -- CREB cAMP response element binding protein -- HDAC histone deacetylases -- NAc nucleus accumbens -- NAD nicotinamide adenine dinucleotide -- PFC prefrontal cortex -- VPA Voluntary physical activity; conditioned place preference -- ethanol -- voluntary physical activity -- running wheels -- CREB -- SIRT; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2021.06.029
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Voluntary physical activity prevents ethanol rewarding effects. Voluntary physical activity and ethanol reduce CREB activation in the NAc. CREB levels are positively correlated with ethanol rewarding effects in the NAc. Voluntary physical activity reduces SIRT-1 levels in the NAc. 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.