A translational systems biology approach in both animals and humans identifies a functionally related module of accumbal genes involved in the regulation of reward processing and binge drinking in males.

Background: The mesolimbic dopamine system, composed primarily of dopaminergic neurons in the ventral tegmental area that project to striatal structures, is considered to be the key mediator of reinforcement-related mechanisms in the brain. Prompted by a genome-wide association meta-analysis implicating the Ras-specific guanine nucleotide-releasing factor 2 (RASGRF2) gene in the regulation of alcohol intake in men, we have recently shown that male Rasgrf2(-/-) mice exhibit reduced ethanol intake and preference accompanied by a perturbed mesolimbic dopamine system. We therefore propose that these mice represent a valid model to further elucidate the precise genes and mechanisms regulating mesolimbic dopamine functioning.

Oxytocin receptor genotype modulates ventral striatal activity to social cues and response to stressful life events.

Background: Common variants in the oxytocin receptor gene (OXTR) have been shown to influence social and affective behavior and to moderate the effect of adverse experiences on risk for social-affective problems. However, the intermediate neurobiological mechanisms are not fully understood. Although human functional neuroimaging studies have reported that oxytocin effects on social behavior and emotional states are mediated by amygdala function, animal models indicate that oxytocin receptors in the ventral striatum (VS) modulate sensitivity to social reinforcers.

Neural mechanisms of attention-deficit/hyperactivity disorder symptoms are stratified by MAOA genotype.

Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by deficits in reward sensitivity and response inhibition. The relative contribution of these frontostriatal mechanisms to ADHD symptoms and their genetic determinants is largely unexplored.

Methods: Using functional magnetic resonance imaging and genetic analysis of the monoamine oxidase A (MAOA) gene, we investigated how striatal and inferior frontal activation patterns contribute to ADHD symptoms depending on MAOA genotype in a sample of adolescent boys (n = 190).