Abstract
Rationale
Chronic stress exposure disrupts the medial prefrontal cortex’s (mPFC) ability to regulate impulses, leading to the loss of control over alcohol drinking in rodents, emphasizing the critical role of this forebrain area in regulating alcohol consumption. Moreover, chronic stress exposure causes lateralization of mPFC functions with volumetric and functional changes, resulting in hyperactivity in the right hemisphere and functional decrease in the left.
Objectives
This study investigated the inhibitory role of the left prelimbic cortex (LPrL) on ethanol consumption induced by chronic social defeat stress (SDS) in male mice and to examine if inactivation of the LPrL causes disinhibition of the right mPFC, leading to an increase in ethanol consumption. We also investigated the role of lateralization and neurochemical alterations in the mPFC related to ethanol consumption induced by chronic SDS. To this end, we examined the activation patterns of ΔFosB, VGLUT2, and GAD67 in the left and right mPFC.
Results
Temporarily blocking the LPrL or right PrL (RPrL) cortices during acute SDS did not affect male mice’s voluntary ethanol consumption in male mice. When each cortex was blocked in mice previously exposed to chronic SDS, ethanol consumption also remained unaffected. However, male mice with LPrL lesions during chronic SDS showed an increase in voluntary ethanol consumption, which was associated with enhanced ΔFosB/VGLUT2-positive neurons within the RPrL cortex.
Conclusions
The results suggest that the LPrL may play a role in inhibiting ethanol consumption induced by chronic SDS, while the RPrL may be involved in the disinhibition of ethanol consumption.
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Funding
LC-d-S was a recipient of the São Paulo Research Foundation—FAPESP scholarship (2016/08665–0). DB-d-S was a recipient of the Coordination for the Improvement of Higher Education Personnel—CAPES (88887.194785/2018–00) scholarship. RN-d-S (306556/2015–4) and CP (306557/2015–0) were recipients of the National Council for Scientific and Technological Development—CNPq research fellowship.
Fundação de Amparo à Pesquisa do Estado de São Paulo,2016/08665-0,Lucas Canto-de-Souza,Coordenação de Aperfeiçoamento de Pessoal de Nível Superior,88887.194785/2018-00,Daniela Baptista-de-Souza,Conselho Nacional de Desenvolvimento Científico e Tecnológico,306556/2015-4,Ricardo Luiz Nunes-de-Souza,306557/2015-0,Cleopatra Planeta
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All experimental protocols were conducted according to the ethical principles of the Brazilian National Council for the Control of Animal Experimentation (CONCEA) and approved by the local Research Ethics Committee (CEUA/FCF-UNESP: 32/2016).
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Canto-de-Souza, L., Baptista-de-Souza, D., Nunes-de-Souza, R.L. et al. Distinct roles of the left and right prelimbic cortices in the modulation of ethanol consumption in male mice under acute and chronic social defeat stress. Psychopharmacology 241, 1161–1176 (2024). https://doi.org/10.1007/s00213-024-06550-8
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DOI: https://doi.org/10.1007/s00213-024-06550-8