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Cocaine Addiction

Cocaine AddictionA great amount of research has been devoted to understanding cocaine addiction and how it produces its pleasurable effects. One mechanism is through its effects on structures deep in the brain. A regulatory protein best known for its role in a rare genetic brain disorder also may play a critical role in cocaine addiction, according to a recent study in rats. The study was funded by the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health, and published Sunday, Aug. 15 2010 in the journal Nature Neuroscience.

Researchers at the Scripps Research Institute in Jupiter, Fla. found that cocaine consumption increased levels of a regulatory protein called MeCP2 that shuttles back to the nucleus to influence gene expression in the brains of rats. As levels of MeCP2 increased in the brain, so did the animals’ motivation to self-administer cocaine. This suggests that MeCP2 plays a crucial role in regulating cocaine intake in rats and perhaps in determining vulnerability to addiction.

“This discovery, using an animal model of addiction, has exposed an important effect of cocaine at the molecular level that could prove key to understanding compulsive drug-taking,” said Dr. Nora D. Volkow, director of NIDA. “It should open up new avenues of research on the causes and ways to counter the behavioral changes linked to addiction in humans.”

This is the second time this year that a critical factor related to cocaine self-administration in rodents has been identified. In a study published in July in the journal Nature, Scripps researchers identified regulatory molecule miRNA-212 as playing a key role in cocaine intake. However, MeCP2 increased motivation for cocaine, whereas miRNA-212 had the opposite effect, suggesting that the latter plays a protective role against drug seeking.

In the current study, researchers discovered that the brain’s balance between MeCP2 and miRNA-212 ultimately regulates cocaine intake. When the balance shifts toward MeCP2, cocaine intake increases. When the balance shifts toward miRNA-212, cocaine intake decreases. What determines the balance is not yet understood, however, and will be the focus of future research.

“This study represents another piece in the puzzle of determining vulnerability to cocaine addiction,” said Paul J. Kenny, senior author on the study and an associate professor at Scripps. “If we can continue putting the pieces together, we may be able to determine whether there are viable treatments for this condition.”

Another research study on cocaine addiction revels that scientists have discovered regions within the brain that, when stimulated, produce feelings of pleasure. One neural system that appears to be most affected by cocaine originates in a region, located deep within the brain, called the ventral tegmental area (VTA). Nerve cells originating in the VTA extend to the region of the brain known as the nucleus accumbens, one of the brain's key pleasure centers. In studies using animals, for example, all types of pleasurable stimuli, such as food, water, sex, and many drugs of abuse, cause increased activity in the nucleus accumbens.

Researchers have discovered that, when a pleasurable event is occurring, it is accompanied by a large increase in the amounts of dopamine released in the nucleus accumbens by neurons originating in the VTA. In the normal communication process, dopamine is released by a neuron into the synapse (the small gap between two neurons), where it binds with specialized proteins (called dopamine receptors) on the neighboring neuron, thereby sending a signal to that neuron. Cocaine addiction interferes with this normal communication process. For example, scientists have discovered that cocaine blocks the removal of dopamine from the synapse, resulting in an accumulation of dopamine. This buildup of dopamine causes continuous stimulation of receiving neurons, probably resulting in the euphoria commonly reported by individuals with a cocaine addiction. Because cocaine is extremely addictive, the first-time user cannot possibly predict when loss of control will occur.

Through continued use of cocaine the abuser will often develop a tolerance to the affects. For the brain to experience the same level of pleasure, higher doses and more frequent use of cocaine will become necessary. Individuals recovered from cocaine addiction reported that thoughts of the euphoria experienced from the use of cocaine might possibly cause a tremendous craving and relapse, even after long periods of being without the drug. Attempts to stop using cocaine can fail simply because the resulting depression can be overwhelming, causing the addict to use more cocaine in an attempt to overcome his depression. Through the use of sophisticated technology, scientists can actually see the dynamic changes that occur in the brain as an individual takes the drug. They can observe the different brain changes that occur as a person experiences the "rush," the "high," and, finally, the craving of cocaine. They can also identify parts of the brain that become active when an individual with a cocaine addiction sees or hears environmental stimuli that trigger the craving for cocaine. This overpowering cocaine addiction can cause the addict to do anything to get the drug.

Researchers have found that cocaine stimulates the brain's reward system inducing an even greater feeling of pleasure than natural functions. In turn, its influence on the reward circuit can lead an user to bypass survival activities and repeat drug use. Chronic cocaine use can lead to a cocaine addiction and in some cases damage the brain and other organs. An addict will continue to use cocaine even when faced with adverse consequences.

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