Reward, interrupted: Inhibitory control and its relevance to addictions

Despite an extensive body of fundamental, preclinical and clinical research describing the genetic, molecular, cellular and neural circuitry mechanisms that subserve the motivation to seek and consume drugs of abuse, comparatively little is known about the mechanisms of self-control, which allow organisms to engage in planned, voluntary abstinence from drug abuse. Self-control mechanisms allow organisms to avoid risky drug misuse to begin with, and they are essential to understanding the eventual transition from active drug abuse to sobriety. Research in laboratory animals and human subjects have converged on the notion that inherited variation in the functional complement of dopamine D2-like receptors within frontostriatal regions is associated with poor inhibitory self-control and associated risk for escalated drug and alcohol use. The pharmacological effects of these agents further reduces D2-mediated signaling and further erodes self-control. This talk will highlight dopamine D2 receptors as a mechanistic "bottleneck", linking genetic and environmental risk factors for substance abuse with the phenotypic consequences of loss of self-control that underlie compulsive, clinically impairing addictive behaviors.