| Description |
Antisocial behavior (ASB) is characterized by aggression, violence, drug use, thrillseeking behavior, and delinquent behavior. While childhood and adolescent maltreatment contribute to the ontogeny of this condition, converging evidence suggests that genetic factors play an equally important role. The best-characterized gene shaping ASB predisposition, MAOA, encodes the enzyme Monoamine oxidase A. Low-activity MAOA alleles (MAOA-L) eludes to an elevated risk for ASB development, particularly in males with a history of child abuse and neglect. Evidence on this gene x environment (GxE) interaction in females, however, remains more controversial. To study the biological factors underlying this GxE interaction, our lab established MAOANeo mice, a new line of mice harboring a low-activity MAOA genotype, and subjected them to an early-life stress (ES) regimen simulating child abuse and neglect. These animals develop high levels of aggression from their fourth week of postnatal life onward. Previous data showed that MAOANeo pups exposed to this early stress exhibit early phenotypic predictors of ASB also observed in humans, such as a reduction in resting heart rate. Here, we developed new behavioral paradigms to verify whether additional predictors (such as social deficits and anxiety-like responses) may be found in ES-exposed MAOANeo pups. After optimizing these models for behavioral assessment in pups, we began studying the effects of the interaction of MAOA genotypes, ES, and sex on social interaction and anxiety-like behaviors. Although our research progress was negatively impacted by COVID-19, our preliminary results led to the identification of several effects: first, we found that females exhibit higher anxiety-like responses than males from the end of the first week of life; second, we documented that early stress increased anxietylike responses during the same developmental stage, irrespective of genotype or sex. Finally, our results confirmed that MAOANeo mice exhibit social deficits already from postnatal day 6. Further research will be needed to fully characterize the effects of the interactions between MAOA low activity genotype, early stress, and sex in early developmental stages; however, our newly-developed tools for behavioral assessment in mouse pups hold great promise to extend our current characterization of early predictors of ASB or other neurodevelopmental problems. |
