The Opponent Process theory of motivation states that any stimulus is capable of inducing diametrically opposite and temporarily dissociated actions. Consistent with this theory, animals traversing a straight-arm alley for intravenous cocaine develop approach-avoidance behavior about entering an environment that has been paired with cocaine, demonstrating that the drug possess mixed positive and negative consequences. While the euphoric nature of cocaine has been extensively reviewed in the literature, considerably less is known about the negative effects of cocaine. The intent of this dissertation was to investigate how the opponent process actions of cocaine-paired cues differentially contribute to drug-seeking behaviors after periods of drug withdrawal. Five studies were designed and executed to address three broad aims: (1) to investigate the relative persistence of the positive and negative associations of cocaine-paired cues in acute models of drug administration; (2) to examine the impact of prior daily extended access to cocaine (a model of addiction) on the sensitivity to the dual and opposing actions of the drug; and (3) to identify anatomical regions associated with the positive or negative effects of the drug. The results of these experiments are reviewed in the context of the current literature on the underlying neurobiology of relapse.