Reinforcement learning detuned in addiction: integrative and translational approaches

Abstract

Suboptimal decision-making strategies have been proposed to contribute to the pathophysiology of addiction. Decision-making, however, arises from a collection of computational components that can independently influence behavior. Disruptions in these different components can lead to decision-making deficits that appear similar behaviorally, but differ at the computational, and likely the neurobiological, level. Here, we discuss recent studies that have used computational approaches to investigate the decision-making processes underlying addiction. Studies in animal models have found that value updating following positive, but not negative, outcomes is predictive of drug use, whereas value updating following negative, but not positive, outcomes is disrupted following drug self-administration. We contextualize these findings with studies on the circuit and biological mechanisms of decision-making to develop a framework for revealing the biobehavioral mechanisms of addiction.

Keywords: amygdala; decision-making; dopamine; mGlu5; nucleus accumbens; orbitofrontal cortex.

Figure 1:. Biobehavioral mechanisms mediating the emergence and persistence of addiction-relevant behaviors.

Left, drug use susceptibility: Neurodevelopmental deviations – possibly driven by early life experiences, genetics, or sex hormones – may disrupt the formation of select neural circuits (e.g., amygdala-OFC) and impact the signaling mechanisms (e.g., midbrain D3 receptor expression) that control the degree of value updating that occurs following a positive outcome. Impairments in positive-feedback updating that lead to inflexible patterns of decision-making may accelerate escalation in drug use and, therefore, the development of inflexible patterns of drug use. Right, drug use consequences: Persistent exposure to drugs of abuse, however, alters a different set of neural circuits (e.g., OFC-NAc) and signaling mechanisms (e.g., mPFC mGlu5) that control the degree of value updating that occurs following a negative outcome. Drug-induced disruptions in negative-feedback updating may lead to drug-taking behaviors that appear insensitive to negative consequences and, therefore, could lead to compulsive behavior. The transition between susceptibility and addiction is likely to be governed by various factors (pink box), including age of initial drug use, duration of drug use, patterns of drug taking, and cycles of abstinence/use. Dashed boxes and lines represent outstanding questions and/or relationships that could be examined in future investigations.