Protein alterations in the brain’s reward system during withdrawal leads to incubation of cocaine craving

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Protein alterations in the brain’s reward system during withdrawal leads to incubation of cocaine craving

Protein alterations in the brain’s reward system during withdrawal leads to incubation of cocaine craving

The risk of relapse is a major obstacle to the long-term treatment of patients suffering from drug addiction. Therefore, the need of the hour is to focus on finding a relevant way to identify the targets to treat addiction. Substantial research and studies have been undertaken in recent times to improve the overall understanding related to the role of molecular signaling pathways in triggering drug-induced maladaptations.

In 1986, Gawin F. and Kleber H. proposed that cue-induced cocaine craving increases progressively during the early phase of abstinence and remains high for an extended period. This phenomenon termed as “incubation of drug craving” occurs in animals too. In recent times, a number of scientists found that environmental enrichment plays a pivotal role in reducing the incubation of cocaine craving. During the phase of arbitrary abstinence, environmental enrichment reduced the incentive motivational effects of cocaine in users. This finding indicates that underlying neural mechanisms responsible for triggering cocaine addiction is reversible.

Over the last one decade, great steps have been taken on cocaine addiction in the domain of translational research. The current evidence shows that cocaine produces psychoactive and addictive effects due to the phosphorylation of extracellular signal-regulated (pERK) in the central amygdala (CeA).  Therefore, the CeA neuronal activation serves is responsible for the incubation of craving of both drug and nondrug rewards. In addition, an initial, short-term effect—a buildup of the neurochemical dopamine—gives rise to excitement and a desire to take the drug again. The persistent use of cocaine exacerbates both short-term and intermediate-term effects that may persist for long and may turn out to be irreversible.

Biological factors responsible for increasing cocaine craving

The brain imaging studies in humans have highlighted that regular drug use leads to neuroplastic changes in the glutamatergic inputs to the striatum and midbrain dopamine neurons. This increases the reactivity of the brain to drug cues and lowers the sensivity to nondrug rewards. Consequently, it weakens the self-regulation of users and heightens the risk of a relapse.

Study suggests that most drugs of abuse exert their initial reinforcing effects by activating reward circuits in the brain. Dopamine neurons located in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc) play a key role in the processing of reward-related stimuli, including those associated with the drugs of abuse. It has been suggested that over the first few weeks of withdrawal from cocaine, users become sensitized to drug-associated environmental cues that act as external stimuli for craving. Though  the onset of craving is delayed, it does not decay. Instead, it increases progressively, over a two-month withdrawal period. Hence, cocaine craving intensifies over a period when most of the neuroadaptations that accompany withdrawal from chronic cocaine addiction are in progressive decline.

The drug-related mechanisms fabricating collective variations in neurotransmission are sometimes epigenetic in nature. While there is no change in a person’s genes, drugs can nudge few genes to increase or decrease the production of proteins, leading to variations in neuron function or even actual reshaping of the physical structure of neurons. For example, in mice, cocaine alters important genetic transcription factors and the expression of hundreds of genes. The chronic abuse of cocaine massively alters the production of proteins in the neurons of the brain’s reward system, which is responsible for replacing voluntary behavior with compulsive drug-seeking behavior.

Recovery from drug addiction is possible

The above findings enhance the understanding of the dilemmas of people suffering from drug addiction. It is possible to recover from drug or alcohol addiction provided one is willing to seek help. The families and friends can be a great source of support by encouraging the affected person to walk the path of sobriety by getting professional treatment at the earliest. Untreated substance abuse problems are detrimental to not just the user’s health but also to his or her life.

If you or your loved one is battling any form of drug addiction, contact the Arizona Drug Addiction Helpline to get connected to some of the reputed drug addiction treatment centers in Arizona and other parts of the country. Call our 24/7 helpline number 866-576-4147 or chat online with one of our specialists to know more.

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