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.
Highlights
Addiction is characterized by a transition from recreational drug use to compulsive, disordered use, punctuated by cycles of abstinence, withdrawal, craving, and relapse
Together these results suggest that the nigrostriatal DA pathway is recruited to promote the escalation of drug use and rigid drug-intake patterns, which underlies the development of addiction-like states in substance use disorder (SUD)
Dopamine innervation to the striatum contributes to multiple, parallel functions in the context of addiction-like behavior, with the mesostriatal pathway providing a “pull” toward drug seeking by signaling drug and drug-associated stimulus value, especially early in the use cycle
Summary
Addiction is characterized by a transition from recreational drug use to compulsive, disordered use, punctuated by cycles of abstinence, withdrawal, craving, and relapse. Features of human drug use are complicated by social and political factors, including stigmatization, criminalization, and barriers to treatment access. SUDs are characterized by pharmacological effects of tolerance and withdrawal, as well as a core set of behavioral features defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). These can be grouped into three major categories: I. Research making use of non-human animals is essential to this effort. Leveraging convergent biology of reward learning and decision-making systems across species, addiction scientists have established a variety of animal models to investigate drug-related behaviors (Figure 1). While considerable debate exists surrounding the translational efficacy of individual models to the complexity of human addiction (for recent review, see Venniro et al, 2020), they
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