The Influence of Ethanol on Maternal Behavior and Offspring: Exploring the Behavioral and Neural Protective Mechanisms of Environmental Enrichment

Abstract

Alcohol consumption by pregnant women is a serious public health issue. Besides the harm it can cause to the mother, alcohol can cross the placental barrier and affect fetal development. Alcohol exposure can result in direct effects on the fetus, and its consumption during pregnancy can also interfere with the bond between the mother and the offspring, possibly reducing maternal oxytocin release. On the other hand, our studies with experimental animals have shown that environmental enrichment (EE) during pregnancy prevented impairments in maternal behaviors towards offspring (FAPESP Processes 2021/04816-1 and 2017/13756-7). They also demonstrated that EE can modulate the oxytocin system, increasing oxytocin concentrations and mRNA in the hypothalamus in male animals (FAPESP Process 2015/02397-0, Rae et al., 2018; Rae et al., submitted). Oxytocinergic neurons project to brain regions, including the medial preoptic area (MPOA) of the hypothalamus, important for the manifestation of maternal behavior. In addition to oxytocin itself, there are modulators of the oxytocinergic system capable of influencing maternal behavior, such as dopamine (Stolzenberg et al., 2007) and estrogen (Siegel, Rosenblatt, 1975). Activation of D1 receptors in MPOA efferents or activation of these receptors in the nucleus accumbens promotes the onset of maternal behavior, and hormonal and environmental variations affect this behavior.In this study, our goal is to evaluate possible mechanisms through which EE during pregnancy can prevent alcohol-related impairments in maternal behavior and offspring development, focusing on the oxytocinergic system, as our laboratory is a pioneer in these studies. For this purpose, female Swiss mice will be divided into 4 groups according to the type of housing during pregnancy (standard or enriched) and treatment (water or ethanol [3 g/kg]; administered by gavage). First, we will assess whether EE can alter ethanol metabolism, through measurements of alcohol concentration in the blood and hepatic enzyme activity of the mother and offspring. Next, we will investigate the effects of EE on the oxytocinergic system during pregnancy, through measurements of oxytocin gene expression in the hypothalamus, as well as the expression of estradiol receptors (ER± and ²) in the medial preoptic area. Furthermore, we will investigate the activity of dopaminergic neurons in the context of maternal behavior using fiber photometry. Additionally, we will assess potential epigenetic changes in the oxytocin receptor of the offspring.Therefore, our research aims to elucidate potential oxytocinergic or dopaminergic mechanisms through which exposure to alcohol during pregnancy may offer protection against the harmful effects of alcohol on maternal behavior." (AU)