Addiction: beyond dopamine reward circuitry. Volkow ND, Want G-J, Fowler JS, Tomasi D, Teland F. 11 Research suggests that cocaine elevates stress hormones, inducing neuroadaptations that further increase sensitivity to the drug and cues associated with it.
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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. 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 The stress circuits of the brain are distinct from the reward pathway, but research indicates that there are important ways that they overlap. Stress can contribute to cocaine relapse, and cocaine use disorders frequently co-occur with stress-related disorders. 9Īlthough addiction researchers have focused on adaptations in the brain’s reward system, drugs also affect the brain pathways that respond to stress. 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.
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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.
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Animal studies show that cocaine exposure can cause significant neuroadaptations in neurons that release the excitatory neurotransmitter glutamate. Use of cocaine, like other drugs of abuse, induces long-term changes in the brain.