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Cocaine’s Long-Term Effects on the Brain

Use of cocaine induces long-term changes in the brain.

With repeated exposure to cocaine, the brain starts to adapt so that the reward pathway becomes less sensitive to natural reinforcers. At the same time, circuits involved in stress become increasingly sensitive, leading to increased displeasure and negative moods when not taking the drug, which are signs of withdrawal. These combined effects make the user more likely to focus on seeking the drug instead of relationships, food, or other natural rewards.

Stress Pathways

Stress can contribute to cocaine relapse, and cocaine use disorders frequently co-occur with stress-related disorders. The stress circuits of the brain are distinct from the reward pathway, but there are important ways that they overlap. The ventral tegmental area seems to act as a critical integration site in the brain that relays information about both stress and drug cues to other areas of the brain, including ones that drive cocaine-seeking. Animals that have received cocaine repeatedly are more likely to seek the drug in response to stress, and the more of the drug they have taken, the more stress affects this behavior. Research suggests that cocaine elevates stress hormones, inducing neuroadaptations that further increase sensitivity to the drug and cues associated with it.

The Orbitofrontal Cortex

Chronic cocaine exposure affects many other areas of the brain too. For example, animal research indicates that cocaine diminishes functioning in the orbitofrontal cortex (OFC), which appears to underlie the poor decision-making, inability to adapt to negative consequences of drug use, and lack of self-insight shown by people addicted to cocaine. A study using optogenetic technology, which uses light to activate specific, genetically-modified neurons, found that stimulating the OFC restores adaptive learning in animals. This intriguing result suggests that strengthening OFC activity may be a good therapeutic approach to improve insight and awareness of the consequences of drug use among people addicted to cocaine.