Dopaminergic signaling of uncertainty and the aetiology of gambling addiction.

Although there is increasing clinical recognition of behavioral addictions, of which gambling disorder is the prototype example, there is a limited understanding of the psychological properties of (non-substance-related) behaviors that enable them to become 'addictive' in a way that is comparable to drugs of abuse. According to an influential application of reinforcement learning to substance addictions, the direct effects of drugs to release dopamine can create a perpetual escalation of incentive salience. This article focusses on reward uncertainty, which is proposed to be the core feature of gambling that creates the capacity for addiction. We describe the neuro-dynamics of the dopamine response to uncertainty that may allow a similar escalation of incentive salience, and its relevance to behavioral addictions. We review translational evidence from both preclinical animal models and human clinical research, including studies in people with gambling disorder. Further, we describe the evidence for 1) the effects of the omission of expected reward as a stressor and to promote sensitization, 2) the effect of the resolution of reward uncertainty as a source of value, 3) structural characteristics of modern Electronic Gaming Machines (EGMs) in leveraging these mechanisms, 4) analogies to the aberrant salience hypothesis of psychosis for creating and maintaining gambling-related cognitive distortions. This neurobiologically-inspired model has implications for harm profiling of other putative behavioral addictions, as well as offering avenues for enhancing neurological, pharmacological and psychological treatments for gambling disorder, and harm reduction strategies for EGM design.