Clinical and preclinical evidence indicate that the setting of drug use affects drug reward in a substance-specific manner (Caprioli et al. 2009; Badiani and Spagnolo 2013). When heroin and cocaine co-abusers, for example, report on the circumstances of drug use, they indicate distinct settings for the two drugs: heroin being used preferentially at home and cocaine preferentially outside the home (Caprioli et al. 2009; Badiani and Spagnolo 2013). Similar results were obtained in rats given the choice between these two drugs (Caprioli et al. 2007, 2008, 2009). Rats that live in the self-administration (SA) chambers (Resident rats) tend in fact to prefer heroin to cocaine, whereas rats that are transferred to the SA chambers only for the test sessions (Non-Resident rats) tend to prefer cocaine to heroin. The goal of this study was to investigate whether the affective value of cocaine and heroin changes as a function of the setting. It has been shown that rats emit ultrasonic vocalizations (USVs) in the range of 50-kHz when exposed to rewarding stimuli, whereas they emit 22-kHz USVs in the presence of aversive stimuli, suggesting that 50-kHz USVs reflect positive affective states (Burgdorf et al. 2000, 2001, 2008). In the present study, we recorded USVs in rats undergoing cocaine and heroin SA on alternate days. We found that Non-Resident rats emit more 50-kHz USVs when self-administering cocaine than when self-administering heroin. In contrast, Resident rats emit more 50-kHz USVs when self-administering heroin than when self-administering cocaine. These findings indicate that the setting of drug taking exert a substance-specific influence on the ability of drugs to induce a positive affective state
