The biology of addiction

Abstract

In this narrative review, the neurobiological mechanisms underlying substance abuse and addiction are discussed with a particular emphasis on the mechanisms that promote ongoing use and relapse. Addiction is estimated to affect 10-15% or more of the adult population, including physicians. Genetic predisposition, psychological and environmental risk factors, the timing of exposure to the substance, the type of substance used, and the frequency of use influence the individual's susceptibility to addiction. Abused substances act on the brain's reward system, a neural circuit that produces pleasurable feelings in response to stimuli that promote survival, thereby modifying future behavior to seek out similar stimuli. Endogenous activators include food, sex, and social interaction. Drugs of abuse hijack the reward circuit, producing intense activation. Repetitive exposure to substances leads to persistent, altered genetic expression and accumulation of ΔFos-B and corticotropin-releasing factor. High levels of these substances suppress the reward circuit and activate the endogenous stress response, resulting in a generalized state of discord. These changes are enduring and can trigger substance use relapse even after long periods of abstinence.

AMPK signaling in the nucleus accumbens core mediates cue-induced reinstatement of cocaine seeking

“…Repeated exposure to addictive drugs leads to persistent alterations in genetic expression and synaptic and structural plasticity in limbic regions, such as the nucleus accumbens (NAc), and enhances the brain’s reactivity to drug-associated cues 1–3 . These changes are enduring and contribute to drug relapse even after long periods of abstinence 4–7 .…”

Anesthetic implications of recreational drug use

“…This pathway includes dopaminergic neurons extending from the ventral tegmental area to the nucleus accumbens (NAc) and the prefrontal cortex. 12,13 Drugs of abuse, together with natural rewards, such as food, sex, social interaction, and exercise, all increase NAc dopamine levels. This neurochemical response contributes to subjective reward and positive reinforcement.…”

“…Adapted and reproduced with permission from the Minister of Health, 2017 glutamate, gamma-aminobutyric acid, endogenous cannabinoids and opioids, serotonin, and norepinephrine) participate in reward processing and in the neuroadaptations associated with addiction. 13,14 The vulnerability to developing specific addictions may be enhanced or decreased by the presence of specific variants of multiple genes. 15 Genetic predisposition is responsible for about half of a person's risk of becoming addicted, whereas epigenetics (environmental factors) influence the effect of these genes.…”

“…Cela inclut les neurones dopaminergiques allant de l'aire tegmentale ventrale jusqu'au noyau accumbens (NAc) et au cortex préfrontal. 12,13 Les drogues utilisées par les toxicomanes, de la même façon que les gratifications naturelles telles que la nourriture, le sexe, les interactions sociales et l'activité physique, augmentent toutes les taux de dopamine dans le NAc. Cette réponse biochimique cérébrale contribue à la gratification subjective et à un renforcement positif.…”

The physician at risk: disruptive behaviour, burnout, addiction, and suicide

“…Some readers may consider certain of these topics as somewhat taboo, perhaps because of the perception that they are not as organic as other non-mental health-related illnesses. Nevertheless, we need only look to the article on the biology of addiction 3 to see just how science continues to elaborate on the complex etiology and pathophysiology of addiction-related brain disorders.…”