Psychopharmacology (2011) 214:769–778 administration methods (e.g., Bossert et al. 2005; de Wit and Stewart 1983; Leri and Stewart 2001; Shalev et al. 2001; Zhou et al. 2009). It should be noted that reliable response reinstatement of heroin seeking has been reported using the runway model (e.g., Ettenberg and Geist 1993; McFarland and Ettenberg 1997), but these studies included more exposure to heroin during training and/or longer periods of withdrawal to ensure a significant weakening in run times prior to the reinstatement challenge. The current findings are important in that they show that in animals experiencing only modest daily drug exposure (which undoubtedly has relevance for a considerable subset of the human drug-using population), cocaine-paired cues have a stronger impact on potentiating drug-seeking behavior than do heroin-paired cues. This suggests that the development of a more pernicious form of drug use likely has its seeds in early “recreational” use of the drug in question and that the “risk” of abuse may be greater for cocaine than for heroin. A final observation worth noting is what appears to be a time-dependent reduction in retreat frequency (in the cocaine-cue condition) as extinction progressed (Fig. 3, left panel). Although the Group × Trial interaction on those data was only marginal (p < .07), the pattern of behavior observed seems to mirror the “incubation of cocaine craving” phenomenon in which the effectiveness of drug- paired cues to reinstate drug-seeking increases as the period of drug withdrawal is extended (e.g., Ahmed and Cador 2006; Grimm et al. 2001; Lu et al. 2003, 2004; Shalev et al. 2001; Tran-Nguyen et al. 1998; Zhou et al. 2009). The current results suggest the intriguing possibility that the incubation phenomenon may stem, at least in part, from a differential rate at which the negative relative to the positive associations that animals have established between cocaine and cocaine-paired cues weaken over time. Acknowledgments The authors acknowledge, with gratitude, Stephanie Waldroup and Gleb Kichaev for their assistance in various aspects of the project and Dr. Osnat Ben-Shahar for her input on the design and conception of these studies. This research was funded by NIDA grant DA05041 awarded to A.E. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. 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