08 Apr How Cocaine-Related Brain Changes May Increase Risks for Addiction
Like essentially all substances of abuse, cocaine alters normal function in the brain’s pleasure/reward circuitry, commonly known as the limbic system. According to findings reported in 2011 by the National Institute on Drug Abuse, people who habitually use cocaine distort the function of more than 1,000 limbic system proteins. Alteration of at least some of these proteins apparently accounts for much of the transition from voluntary to involuntary drug use that marks the onset of cocaine addiction.
Proteins are molecules made from chemical building blocks called amino acids. Twenty types of these acids are arranged in a vast array of sequences in order to produce literally thousands of unique proteins. Depending on how it’s constructed, a protein molecule can perform a number of vital tasks. One main group of specialized proteins, called enzymes, give the body the ability to trigger the chemical reactions needed to power the cells and carry out an assortment of processes critical to survival.
Limbic System Basics
Limbic system is the collective name for a series of structures located deep within the brain; these structures form a pathway or circuit that produces feelings of pleasure. Specific structures commonly considered to be associated with the limbic system include the hippocampus, which plays a number of roles related to memory; the amygdala, which helps process signals related to pleasure, fear, and other basic motivations; and the nucleus accumbens, which helps regulate pleasurable sensations related to sex and substance use.
In a study published in 2009 in the journal Neuron, a multi-university research team examined the effects of cocaine on the genes that carry instructions for the construction of more than 20,000 proteins produced inside the limbic system’s nucleus accumbens. In the first stage of the study, the researchers gave cocaine to a group of mice for a week. At the end of this time period, roughly 7 percent of the genes in the nucleus accumbens showed signs of unusual alteration.
The researchers then focused on the alterations that cocaine makes in the normal production of two particular enzymes inside the nucleus accumbens, known as SIRT1 and SIRT2. For a number of reasons, they believed that a cocaine-related increase in the production of these two enzymes plays a major role in the onset of drug-seeking behaviors after an initial exposure to cocaine. To test this theory, they injected a group of cocaine-exposed test animals with a substance that increases the brain’s levels of SIRT1 and SIRT2, then examined the animals for signs of drug cravings. When compared to a second group of animals with normal brain levels of SIRT1 and SIRT2, the animals with increased levels of these enzymes showed a much stronger desire to continue cocaine use.
The authors concluded that when cocaine users take the drug repeatedly over time, its effects on SIRT1 and SIRT2 levels play a clear role in the transition from voluntary or casual drug use to compulsive or involuntary drug use.
After drawing their conclusions about cocaine’s effects, the researchers gave their test animals a substance that decreases the production of SIRT1 and SIRT2. When given the opportunity to use cocaine after this treatment, these animals exhibited more than a 50 percent drop in their level of drug interest. In the future, doctors and researchers may be able to develop medication-based treatments that produce the same type of results in humans.
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