Can EE restore the effects of prenatal ethanol exposure?

PAUTASSI R.M.; WILLE-BILLE, ARANZA; DADARIO C.

Congreso; 2022 Virtual Meeting of the Latinamerican Society of Biomedical Research on Alcoholism; 2022

Latinamerican Society of Biomedical Research on Alcoholism

renatal ethanol exposure (PEE) is associated with several deleterious effects, including alterations in gene expression of key systems responsible for processing of ethanol?s motivational effects. We observed that PEE upregulated κ opioid receptors (KOR) mRNA levels in the prefrontal cortex, and prodynorphin (PDYN) and KOR mRNA levels in the ventral tegmental area (VTA), in Wistar rats. Treatments to prevent or reduce the consequences of PEE are scarce. Environmental enrichment (EE) is a non-pharmacological intervention, valuable to reduce the effects of environmental toxins and some psychoactive drugs. The studies that have analyzed the modulation of ethanol?s effects by EE have provided, however, mixed results. Studies conducted in several labs have revealed that EE, applied for a short time during adolescence, results in enhanced ethanol intake or reinforcement, for instance measured via conditioned place preference. After finding these outcomes, we applied a protracted EE protocol, from gestational day 20 to postnatal day 26, to rats that had been exposed (or not, control group) to PEE (2.0 g/kg ethanol, gestational days 17-20). EE ameliorated or normalized a PEE-induced upregulation of KOR gene expression in amygdala, a PEE-induced exacerbation of PDYN gene expression in VTA, and alterations in BDNF mRNA levels in VTA and Nucleus accumbens. EE also normalized PEE-induced lower DNA methylation at the PDYN gene promoter. These results suggest that EE, when applied in a relatively lengthy fashion, can help reverse PEE-induced alterations in gene expression. Future studies should analyze if this protocol can also reduce other effects of PEE.