Neurocircuitry of Addiction

Abstract

Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle composed of three stages: ‘binge/intoxication’, ‘withdrawal/negative affect’, and ‘preoccupation/anticipation’ (craving). Animal and human imaging studies have revealed discrete circuits that mediate the three stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a key role in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex–dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control. The transition to addiction involves neuroplasticity in all of these structures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala. The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.

Antagonists in the medical management of opioid use disorders: Historical and existing treatment strategies

“…OUD is now recognized as a chronic disorder that persists beyond the acute withdrawal period and, therefore, is insufficiently managed with short‐term interventions. Observable neuroadaptive changes in the brain may explain the high levels of relapse that characterize substance use disorders 18. Medications have been developed to address these changes and treat OUD.…”

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

“…In contrast, striatonigral neurons, which project axons to the substantia nigra pars reticulata, can be recognized by the cholinergic muscarinic M4 receptor (M4R) or dopamine D1 receptor (D1R) (Gong et al, 2003;Le Moine and Bloch, 1995;Lobo et al, 2006;Surmeier et al, 1996). This is especially important as striatal-specific neuronal circuits are implicated in several aspects of addictive behaviors (Koob and Volkow, 2010). Anatomically, the striatum can be divided into two distinct sub-regions, the dorsal striatum and the ventral striatum.…”

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

“…Despite these structural and functional differences, drugs of abuse (like natural rewards) share a common characteristic of being reinforcing; humans and animals will work to acquire and consume these substances, rapidly associating environmental and interoceptive cues that predict their availability and increasing the frequency of behaviors required to obtain them (Hyman et al, 2006). Repeated exposure to drugs of abuse can produce the condition of drug addiction, characterized by compulsive drug-seeking and drug-taking behavior that continues despite harmful consequences (Deroche-Gamonet et al, 2004;Koob and Volkow, 2010). A full review of the mechanisms of drug addiction is beyond the scope of this review, but the basic evidence for a neuronal basis of drug reinforcement is provided.…”

“…Despite decades of progress toward understanding the neurobiological consequences of acute and repeated drug exposure, the underlying mechanisms of addiction behavior-including drug-seeking, drug-taking, and relapse behavior following periods of abstinence-remain unsolved. Although drug-induced alterations in neuronal function remain an essential component for theories of drug addiction (Koob and Volkow, 2010), accumulating evidence suggests they are not the only cells impacted by drugs of abuse. Glial cells, including microglia and astrocytes, are also influenced by exposure to abused drugs, and their responses likely contribute to the behavioral outcomes associated with substance abuse (Coller and Hutchinson, 2012;Miguel-Hidalgo, 2009).…”