Efficacy of N-acetylcysteine on the Craving Symptoms of Abstinent Hospitalized Patients with Cocaine Addiction

Cocaine abuse is associated with serious physical, psychiatric and social problems. Addiction results in the compulsive use of a substance with loss of control and persistence despite the negative consequences.The act of re-engaging in the search for drugs is called relapse and a particularly insidious aspect of addiction is that vulnerability to relapse lasts for many years after stopping drug use.

The main reason why people continue to use cocaine is because of its influence on the reward system.Indeed, this substance makes it possible to increase the level of dopamine, particularly in the nucleus accumbens.This increase in dopamine is not related to the hedonic pleasure that consumption provides. Instead, it imprints a positive value to enhancers and facilitates the learning of reward associations through the modulation of the cortical and subcortical regions of the brain.In other words, it suggests that users become sensitive to a series of stimuli that combine with a rewarding feeling, which drives them to consume when they encounter them.

Initial investigations regarding the effect of dopamine on the reward system were conducted primarily on the mesolimbic dopaminergic pathway linking the ventral tegmental area to the nucleus accumbens. More recent work has now recognized the role of mesocortical and mesostriatal pathways, but dopamine is far from being the only neurotransmitter involved.

Glutamate also plays a central role in the neuroadaptive changes resulting from chronic exposure to cocaine. Preclinical research has shown that intense exposure to cocaine increases the extracellular level of glutamate in the nucleus accumbens. Cocaine-induced chronic adaptations to glutamatergic homeostasis within the nucleus accumbens include downregulation of the cystine-glutamate (also called xc) exchanger on glial cells and the glial glutamate transporter 1 (GLT-1).

The cystine-glutamate exchanger is an amino acid anti porter that is generally involved in the exchange of extracellular L-cystine (L-Cys2) and intracellular L-glutamate (L-Glu) across the cell plasma membrane. Existing data indicate that these exchanges being diminished, they contribute to abnormal glutamate signaling in the corticostriatal pathway and that these cocaine-induced changes in the Xc system are necessary to restore consumption behavior in the rodent. This imbalance between synaptic and non-synaptic glutamate in the corticostriatal pathway impairs communication between the prefrontal cortex and the nucleus accumbens. As a result, long-term use of cocaine decreases an individual's ability to inhibit the research and consumption behaviors of the product. This results in a relapse syndrome characteristic of addictions.The Xc system would therefore be a potential therapeutic target for the treatment of cocaine addiction.