Neural Mechanisms of Individual Differences in Cocaine Avoidance

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Abstract: Drugs of abuse, such as cocaine, produce rewarding effects that have been extensively investigated. However, these drugs also produce aversive effects that are far less understood, even though they strongly influence drug‐seeking, and exhibit large individual variability that contributes to differences in individual addiction propensity. We found that aversive responses to cocaine depend critically on serotonin and glutamate signaling in the rostromedial tegmental nucleus (RMTg), a major afferent to midbrain dopamine neurons. This proposal examines cellular mechanisms by which these receptors drive neural activation and aversive conditioning, and why these responses occur much more strongly in some individuals than others, with an overall aim of identifying novel potential therapeutic targets for regulating drug‐seeking and treating addiction.