Full Length ArticlePrenatal exposure to alcohol impairs social play behavior in adolescent male mice
Introduction
Alcohol consumption during pregnancy is a serious public health problem and a leading cause of developmental and behavioral disabilities (Abel and Dintcheff, 1978; Lemoine et al., 2003). The adverse effects of alcohol on the developing fetus result in a spectrum of structural abnormalities, behavioral defects, and neurocognitive disabilities that are diagnosed as fetal alcohol syndrome (Barr and Streissguth, 2001; Lange et al., 2017; Roozen et al., 2016; Sowell et al., 2018).
Although most reports on alcohol neurobehavioral toxicity are related to the consumption of high amounts of alcohol during pregnancy, previous research suggests that prenatal exposure to moderate amounts of alcohol also has deleterious outcomes in children (Sood et al., 2001; Marquardt and Brigman, 2016). In addition, it has been systematically demonstrated that prenatal alcohol exposure alters multiple neurotransmitter and neuromodulatory systems throughout the brain, even in low levels of exposure, leading to significant neurobehavioral alterations in rodent offspring (Meyer and Riley, 1986; Valenzuela et al., 2012; Cullen et al., 2013; Mamluk et al., 2017; Shahrier and Wada, 2018). Previous studies have shown that developmental alcohol exposure affects areas of the brain such as the prefrontal cortex (PFC), which are important for the processing of social cues (Euston et al., 2012; Skorput and Yeh, 2016), as such, the purpose of this study was to evaluate the impact of prenatal exposure to small amounts of alcohol on the social play behavior in adolescent offspring.
Additionally, disruption in the maternal-pup dyad behavior is known to have a critical impact on pups’ long-term development and socio-emotional behavior (Kelly et al., 2009). However, it is not clear whether the behavioral changes seen in both mothers and infants are caused by alcohol-related effects in the infants or by inherent features in mothers who engage in social drinking during pregnancy, or a combination of both. Therefore, the aim of this study was twofold. To test (1) whether low levels of prenatal alcohol exposure adversely affect offspring behavior during adolescence by changing the activation pattern of brain areas related to such behavior and (2) whether these effects are a result of alterations in maternal behavior or a direct consequence of alcohol on offspring during prenatal development.
Section snippets
Animals
Adult Swiss nulliparous female and male mice (9 weeks of age) were obtained from the Central Animal Facility of the Federal University of Alfenas and housed in a temperature-controlled room (22 °C) on a 12:12-h light-dark cycle (lights on at 7:00 h), with ad libitum access to water and standard laboratory mice food. All experimental procedures followed the ethical principles in animal research adopted by the Ethics Committee on the Use of Animal of Federal University of Alfenas (protocol
Results
Although the total calorie intake in the alcohol and pair-fed groups was 89.4% that of the ad libitum control group, this was not reflected in the maternal body weight of the alcohol- and pair-fed groups during gestation (diet factor: F2,196 = 0.03, p = 0.96, ω2 = 0.003; gestational days factor: F6,196 = 375.8, p < 0.001, ω2 = 0.86; interaction diet x gestational days: F12,196 = 0.24, p = 0.99, ω2 = 0.0001; Fig. 1). The average consumption of ethanol in the alcohol group was 1.29 ml/day/mice,
Discussion
The current study showed that prenatal alcohol exposure at a low dose has an important long-term implication for offspring behavior. We demonstrated that low prenatal alcohol exposure decreases both social play behavior in adolescent offspring and neuronal activation in the prefrontal cortex. Additionally, we report that these results are not influenced by alteration in maternal behavior of dams during lactation, suggesting a direct effect of low prenatal alcohol exposure on such findings. To
Credit author statement
Dr M A Ávila participated in study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content. Dr L. D. Cabral participated in immunohistochemistry assay. R. M. Gonçalvez and E.C. Nascimento participated in acquisition of behavioral data. Dr F.C. Vilela and Dr A. Giusti-Paiva participated in study concept and design, acquisition of data, analysis and interpretation of data,
Declaration of competing interest
The authors declare no conflict of interest.
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgements
We are grateful for the excellent technical support offered by José dos Reis Pereira. This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG#03346/2018, AG-P) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #308762/2017-7; AG-P). M. A Ávila received graduate fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
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