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Stress and drug-associated cues can trigger drug desire and relapse in abstinent cocaine users. Although the role of these two factors in relapse is well documented, it remains unclear as to whether an interaction between stress and drug-associated cues can lead to an enhancement in cocaine-seeking behavior. Here, we assessed the effects of the anxiogenic α₂-noradrenergic receptor antagonist, yohimbine, on reinstatement of cocaine-seeking in rats either in the presence or absence of cocaine-associated cues. Yohimbine pretreatment in the absence of cocaine-associated cues or cues by themselves reliably reinstated responding on the previously cocaine-paired lever (3–4 times higher than extinction levels). However, animals showed greatly potentiated responding if yohimbine preceded cue-induced reinstatement (10–13 times higher than extinction levels, or 3–5 times over cues or yohimbine alone). While …