Cocaine use alters gene expression in brain reward circuits study finds

A study published in the journal of biological psychiatry has reviewed unique genetic changes in the brain reward pathways in brains associated with cocaine use. This includes mice brains of first time users, mice withdrawing from the drug and mice being re-exposed to the drug after not using for a period of time. The findings of the study provide unique insight into how cocaine affects gene expressions, especially at a molecular level.

The study is the first of its kind, researchers in the study allowed mice to self-administer cocaine as a model of human addiction. Gene expression changes were associated with addiction-like behaviours.

John Krystal, the editor of Biological Psychiatry, said “This study elegantly highlights the complexity of the brain’s molecular response to self-administered cocaine, pointing to mechanisms that might be targeted by treatments,”

Key points

• Researchers looked at differences in gene expression when mice were first exposed to cocaine. In cocaine-addicted mice after a short (24 hours )or long (30 days period of withdrawing from the drug.
• They then looked at gene expression when the mice were re-exposed to cocaine after withdrawing from the drug. This allowed the researchers to examine how gene expression across the brain changes over time as a result of volitional intake of the drug.
• The changes were in the same direction increased or decreases throughout the reward pathway.
• The size of the differences depends on the condition where the mice were in the life cycle of cocaine administration.

Upon analysis, the researchers found changes in many transcripts involved in critical biological processes. The study also reviewed several molecules that are responsible for regulating the expression of the genes associated with addiction.


What experts are saying about drug addiction


Cocaine is a psychoactive alkaloid of the coca plant. Cocaine is the only naturally occurring anaesthetic. Unlike amphetamines, which resemble the structural formula of dopamine and noradrenaline, cocaine has a similar structure to other synthetic sedatives. Cocaine is well absorbed when administered via the mucous membranes, the GI tract and intravenously. Peak concentration happens within five minutes after intravenous injection while the peak levels from smoking usually are reached within 60 minutes.

Some cocaine is excreted in urine unchanged, the majority is metabolised into benzoylecgonine, ecgonine methyl ester, norcocaine and other metabolites. Although cocaine has a short half-life, the elimination half-life of the metabolites last longer. Studies also show that the half-life of cocaine may increase the longer it is used.

Cocaine acts by enhancing the action of dopamine, it does this by blocking its reuptake into the nerve terminal via the transporter and thus increasing the amount of dopamine available. Dopamine is a neurotransmitter that helps controls the brain’ reward and pleasure centres. Dopamine also helps regulate movement and emotional responses. It helps us not just to see rewards, but take action to move towards them. Studies show that people with low dopamine may be more prone to addiction. The presence of specific dopamine receptors is also associated with sensation seeking people.

Cocaine like other drugs has a euphoric and sustained mood elevation effect on the individual taking them. Cocaine increase energy and self-confidence promotes talkativeness, alleviates fatigue and enhances mental alertness. At high doses and during chronic use, feelings of euphoria may be replaced with restlessness, excitability, sleeplessness, loss of libido, nervousness, aggression, suspicion and paranoia, hallucinations and delusional thoughts.

Chronic cocaine use may lead to a range of cardiac complications, for example, acute myocardial infarction and myocardial ischemia are common. Heart attack in constant cocaine use is thought to be caused by increased oxygen demand, vasoconstriction of the coronary artery, increased platelet aggregation and thrombus formation. Also, potential arrhythmias and dysrhythmias may also occur.

Other long-term complications include accelerated atherosclerosis, cardiomyocyte apoptosis, sympathoadrenal-induced myocyte damage, chronic arrhythmias, cardiac hypertrophy and dilated cardiomyopathy. Regular cocaine use has also been associated with many abnormalities in the vascular system of the brain, the most common are haemorrhagic and thromboembolic strokes. Some people are more vulnerable to cocaine-induced excited delirium, symptoms include hyperthermia, extreme behavioural agitation and in some cases, violent behaviours. This may result in collapse or sudden cardiac death.

 

Illicit use of drugs In Australia
• In 2016, around 3.1 million Australians reported using an illegal drug.
• In 2016, the most common illegal drug was cannabis, followed by misuse of pharmaceuticals, cocaine, and then ecstasy.
• While overall use of methamphetamine has decreased, use of crystal methamphetamine (ice) continues to be a problem.
• People who are using crystal methamphetamine (ice), are using it more frequently which increases the risks and harms.

 

 

Source

Elsevier. (2018, May 31). Cocaine use alters gene expression in brain reward circuits: Study investigates transcriptome-wide alterations in response to cocaine self-administration in mice. ScienceDaily. Retrieved June 20, 2018 from http://www.sciencedaily.com/releases/2018/05/180531102706.htm

Winhusen, T. M., Lewis, D. F., Somoza, E. C., & Horn, P. (2014). Pharmacodynamics Must Inform Statistics: An Example from a Cocaine Dependence Pharmacotherapy Trial. ISRN Addiction2014.

 

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