Although cocaine is powerfully rewarding, not all individuals are equally prone to abusing this drug. We postulate that these differences arise in part because some individuals exhibit stronger aversive responses to cocaine that protect against cocaine seeking. Indeed, using conditioned place preference (CPP) and a runway operant cocaine self-administration task, we demonstrate that avoidance responses to cocaine vary greatly between individual "high cocaine-avoider" and "low cocaine-avoider" rats. These behavioral differences correlated with cocaine-induced activation of the RMTg, measured using both in vivo firing and cFos, while slice electrophysiological recordings from VTA-projecting RMTg neurons showed that, relative to low-avoiders, high-avoiders exhibited greater intrinsic excitability, greater transmission via calcium-permeable AMPA receptors (CP-AMPARs), and higher presynaptic glutamate release. In behaving animals, blocking CP-AMPARs in the RMTg with NASPM reduced cocaine avoidance. Hence, cocai...