Neurobehavioral changes arising from early life dopamine signaling perturbations

Abstract

Dopamine (DA) signaling is critical to the modulation of multiple brain functions including locomotion, reinforcement, attention and cognition. The literature provides strong evidence that altered DA availability and actions can impact normal neurodevelopment, with both early and enduring consequences on anatomy, physiology and behavior. An appreciation for the developmental contributions of DA signaling to brain development is needed to guide efforts to preclude and remedy neurobehavioral disorders, such as attention-deficit/hyperactivity disorder, addiction, bipolar disorder, schizophrenia and autism spectrum disorder, each of which exhibits links to DA via genetic, cellular and/or pharmacological findings. In this review, we highlight research pursued in preclinical models that use genetic and pharmacological approaches to manipulate DA signaling at sensitive developmental stages, leading to changes at molecular, circuit and/or behavioral levels. We discuss how these alterations can be aligned with traits displayed by neuropsychiatric diseases. Lastly, we review human studies that evaluate contributions of developmental perturbations of DA systems to increased risk for neuropsychiatric disorders.

Keywords: Dopamine; Neurodevelopment; Neuropsychiatric disorders; Polymorphism; Psychostimulant.