Biological Substrates of Addiction

This review is an introduction to addiction, the reward circuitry, and laboratory addiction models. Addiction is a chronic disease hallmarked by a state of compulsive drug seeking that persists despite negative consequences. Most of the advances in addiction research have centered on the canonical and contemporary drugs of abuse; however, addictions to other activities and stimuli also exist. Substances of abuse have the potential to induce long-lasting changes in the brain at the behavioral, circuit, and synaptic levels. Addiction-related behavioral changes involve initiation, escalation, and obsession to drug seeking and much of the current research is focused on mapping these manifestations to specific neural pathways. Drug abuse is well known to recruit components of the mesolimbic dopamine system, including the nucleus accumbens and ventral tegmental area. In addition, altered function of a wide variety of brain regions is tightly associated with specific manifestations of drug abuse. These regions peripheral to the mesolimbic pathway likely play a role in specific observed comorbidities and endophenotypes that can facilitate, or be caused by, substance abuse. Alterations in synaptic structure, function, and connectivity, as well as epigenetic and genetic mechanisms are thought to underlie the pathologies of addiction. In preclinical models, these persistent changes are studied at the levels of molecular pharmacology and biochemistry, ex vivo and in vivo electrophysiology, radiography, and behavior. Coordinating research efforts across these disciplines and examining cell type- and circuit-specific phenomena are crucial components for translating preclinical findings to viable medical interventions that effectively treat addiction and related disorders. WIREs Cogn Sci 2014, 5:151-171. doi: 10.1002/wcs.1273 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.