Cocaine Research Report
What are some ways that cocaine changes the brain?

Use of cocaine, like other drugs of abuse, induces long-term changes in the brain. Animal studies show that cocaine exposure can cause significant neuroadaptations in neurons that release the excitatory neurotransmitter glutamate.^9,10 Animals chronically exposed to cocaine demonstrate profound changes in glutamate neurotransmission—including how much is released and the level of receptor proteins—in the reward pathway, particularly the nucleus accumbens. The glutamate system may be an opportune target for anti-addiction medication development, with the goal of reversing the cocaine-induced neuroadaptations that contribute to the drive to use the drug.⁹

Although addiction researchers have focused on adaptations in the brain’s reward system, drugs also affect the brain pathways that respond to stress. Stress can contribute to cocaine relapse, and cocaine use disorders frequently co-occur with stress-related disorders.¹¹ The stress circuits of the brain are distinct from the reward pathway, but research indicates that 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.¹¹ 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.¹¹ Research suggests that cocaine elevates stress hormones, inducing neuroadaptations that further increase sensitivity to the drug and cues associated with it.¹¹

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Volkow ND, Want G-J, Fowler JS, Tomasi D, Teland F. Addiction: beyond dopamine reward circuitry. Proc Natl Acad Sci USA. 2011;108(37):15037-15042.

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.¹² 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.¹³