What is addiction?

Definition

An addiction is a cerebral pathology defined by dependence on a substance (heroin, opioids (painkillers, etc.), cocaine, alcohol, cannabis, etc.) or activity (video games, gambling, etc.), with harmful consequences for the health of the person affected. It can be fostered by individual, societal and environmental vulnerability factors.

Impact of opioid, cocaine, amphetamine and cannabis use and addiction: https://ourworldindata.org/illicit-drug-use

sont des pathologies cérébrales définies par une dépendance à une substance ou une activité, avec des conséquences délétères.

Les addictions sont des pathologies cérébrales définies par une dépendance à une substance ou une activité, avec des conséquences délétères.Les addictions sont des pathologies cérébrales définies par une dépendance à une substance ou une activité, avec des conséquences délétères.Les addictions sont des pathologies cérébrales définies par une dépendance à une substance ou une activité, avec des conséquences délétères.Les addictions sont des pathologies cérébrales définies par une dépendance à une substance ou une activité, avec des conséquences délétères.Les addictions sont des pathologies cérébrales définies par une dépendance à une substance ou une activité, avec des conséquences délétères.Les addictions sont des pathologies cérébrales définies par une dépendance à une substance ou une activité, avec des conséquences délétères.Les addictions sont des pathologies cérébrales définies par une dépendance à une substance ou une activité, avec des conséquences délétères.

Les addictions sont des pathologies cérébrales définies par une dépendance à une substance ou une activité, avec des conséquences délétères.

Process

There are several stages, with varying degrees of speed, in the process leading to addiction. What starts out as recreational or occasional use can become more frequent and regular, leading to a loss of control.

Recreation/Social Use

Stage 1 depends on activation of the brain's reward circuit by the substance consumed or activity performed. This releases a neurotransmitter, dopamine, in the nucleus accumbens. The repetition of this consumption, which may be associated with a specific situation, will trigger conditioning in the user, leading to the release of dopamine even before the substance is taken or the activity performed. Reproduction of the situation will thus encourage further use, and this is the start of intoxication.

Example: Coffee and cigarettes in the morning. When a user gets into the habit of smoking a cigarette during or after coffee, dopamine is released when the coffee is prepared. And this anticipation will make the user want to smoke a cigarette after every coffee.

Negative emotional state

Stage 2 is characterized by a loss of sensitivity of the brain's reward circuit to all the molecules that normally stimulate it. This loss of sensitivity is due to a reduction in the level of dopamine released with each consumption. For the substance consumed or the activity performed to bring as much pleasure as before, the quantity must be increased.

What's more, it's not just a question of loss of sensitivity, but also the appearance of a negative emotional state, which is due to changes in the functioning of the amygdala (brain structure). This structure is involved in processing and regulating emotions, as well as in memory formation and storage, including emotional memory. The release of dopamine with each consumption affects the amygdala, exacerbating the negative emotions felt by the user.

Preoccupation/Anticipation

Stage 3 is characterized by a loss of control (craving) in the consumption of substances or activities. Altered reward and emotional circuits lead to changes in processes controlled by the prefrontal cortex, such as self-regulation, decision-making and the ability to resist cravings.

All this helps to explain the frequent relapse of users despite their desire to stop.

The reward circuit and opiates µ-opioid receptor (MOR)

(Welsch and al. 2020). Brain regions are represented as colored squares (orange, binge/intoxication; blue, withdrawal/aversive state; red, preoccupation/anticipation), and MOR expression levels are indicated in light grey to black. (ACA, anterior cingulate cortex; BNST, bed nucleus of the stria terminalis; BLA, basolateral amygdala; CeA, central amygdala; DRN, dorsal raphe nucleus; HIP, hippocampus; InsC, insular cortex; MHb, medial habenula; PFC, prefrontal cortex; NAc, nucleus accumbens; VTA, ventral tegmental area).

The Addictions team is mainly interested in opiates, but also other substances such as cocaine. To study the impact of these substances, we look at the different structures involved in the reward circuit. Our work focuses in particular on the mu (µ) opioid receptor (MOR), which is essential for opioid-induced analgesia and is also responsible for their adverse effects.

MORs in GABAergic interneurons of the ventral tegmental area (VTA) (GABA-MOR) facilitate dopamine release and drug reward. MORs in the striatum, expressed mainly in D1R-type neurons (dopamine D1-like receptor ; D1-MOR), regulate opioid reward and the motivation for opioid consumption. MORs in the medial habenula (MHb) (Chnrb4-MOR) reduce aversive states. Finally MORs in the dorsal raphe nucleus (DRN) drive adaptations leading to depressive-like states and social withdrawal in protracted heroin abstinence (54).

The nucleus accumbens (NAc), amygdala (CeA and BLA), bed nucleus of the stria terminalis (BNST) and DRN are major contributing brain centers in the context of aversive aspects of addiction.