Plasticity associated with escalated operant ethanol self-administration during acute withdrawal in ethanol-dependent rats requires intact matrix metalloproteinase systems

► Intermittent ethanol vapor exposure resulted in escalated operant self-administration for ethanol during acute withdrawal in dependent animals. ► Chronic matrix metalloproteinase (MMP) inhibition during the dependence induction period and acute withdrawal post-dependence testing prevented escalated ethanol self-administration. ► Dependence-induced escalation was shown to be a learned, plasticity-dependent, response because acute MMP inhibition prevented escalated ethanol self-administration.