By Cuong-Alexander To, Pharm.D Candidate 2020; Marco Bortolato, MD Ph.D; Gabriele Floris, Ph.DAbstract The contemporary principle of elucidating antisocial behavior’s (ASB), such as pathological aggression, ontology has mediated by studying complicated gene x environment interactions (GxEi). A well-studied GxEi of pathological aggression occurs between the interplay of low-activity (hypomorphic) alleles of monoamine oxidase A (MAO-A) and childhood maltreatment (early stressors). This study’s aim is to further develop the understanding of the neurobiological mechanisms that contribute to the above mentioned GxEi of pathological aggression for future considerations on innovative targets. As part of ongoing researched on ASB, our research developed a mouse model of GxEi of pathological aggression known as MAO-ANeo Mice: MAO-A hypomorphic transgenic male mice subjected to a semi-random early-life stressor regimen for the first week of life. MAO-ANeo Mice developed overt ASB (aggression, social deficits, and stress response abnormalities), low resting heart rate (an accepted premorbid ASB sign), and significant up-regulation of serotonin receptors 2A (5-HT2aR) in the prefrontal cortex (contributing to the association between stress and serotonergic activity). Corticotrophin releasing factor (CRF) is another neurotransmitter implicated in the role of the GxEi of pathological aggression as it furthers serotonergic activity via decoupling the negative feedback mechanism of 5-HT2aR activation and internalization. Thus, the observation that CRF expression in stressed mice groups were elevated in the prefrontal cortex to evidence that CRF activity may drive 5-HT2aR’s role in the neurobiological mechanism in the GxEi of pathological aggression.