Dopamine Circuit Mechanisms of Addiction-Like Behaviors

Abstract

Addiction is a complex disease that impacts millions of people around the world. Clinically, addiction is formalized as substance use disorder (SUD), with three primary symptom categories: exaggerated substance use, social or lifestyle impairment, and risky substance use. Considerable efforts have been made to model features of these criteria in non-human animal research subjects, for insight into the underlying neurobiological mechanisms. Here we review evidence from rodent models of SUD-inspired criteria, focusing on the role of the striatal dopamine system. We identify distinct mesostriatal and nigrostriatal dopamine circuit functions in behavioral outcomes that are relevant to addictions and SUDs. This work suggests that striatal dopamine is essential for not only positive symptom features of SUDs, such as elevated intake and craving, but also for impairments in decision making that underlie compulsive behavior, reduced sociality, and risk taking. Understanding the functional heterogeneity of the dopamine system and related networks can offer insight into this complex symptomatology and may lead to more targeted treatments.

Keywords: addiction; animal model; dopamine; mesostriatal; nigrostriatal; striatum; substance use disorder.

FIGURE 1

Behavioral models used to classify phenotypes of substance use disorder. (Top) The behavioral criteria of SUDs (circled letters) can be sorted into three main categories: impaired control of substance use (Group I), impaired social behavior (Group II), and risky substance use (Group III). (Left) Common rodent experimental models and the SUD criteria they are thought to best approximate. Note that most models capture multiple SUD features. (Right) Mesostriatal circuits (light purple), including dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAC), and nigrostriatal circuits (dark purple), including dopamine projections to the dorsomedial (DMS) and dorsolateral striatum (DLS), have generally dissociable roles in different components of major SUD models. In the middle panels, the most clearly defined roles for these two systems in each SUD category are listed.