Addiction is considered a disorder that drives individuals to choose drugs at the expense of healthier alternatives. However, chronic cocaine users (CCUs) who meet addiction criteria retain the ability to choose money in the presence of the opportunity to choose cocaine. The neural mechanisms that differentiate CCUs from non-cocaine using controls (Controls) while executing these preferred choices remain unknown. Thus, therapeutic strategies aimed at shifting preferences towards healthier alternatives remain somewhat uninformed. This study used BOLD neuroimaging to examine brain activity as fifty CCUs and Controls performed single- and cross-commodity intertemporal choice tasks for money and/or cocaine. Behavioral analyses revealed preferences for each commodity type. Imaging analyses revealed the brain activity that differentiated CCUs from Controls while choosing money over cocaine. We observed that CCUs devalued future commodities more than Controls. Choices for money as opposed to cocaine correlated with greater activity in dorsal striatum of CCUs, compared to Controls. In addition, choices for future money as opposed to immediate cocaine engaged the left dorsolateral prefrontal cortex (DLPFC) of CCUs more than Controls. These data suggest that the ability of CCUs to execute choices away from cocaine relies on activity in the dorsal striatum and left DLPFC. 1. Introduction A hallmark of addiction is choosing drugs at the expense of healthier alternatives [1]. Historically, research has focused on understanding the mechanisms that give rise to the unwanted choices expressed by chronic cocaine users (CCUs) and treatment efforts have been aimed at stopping them altogether. As with many addictions, stimulant addiction is portrayed as the hijacking of natural valuation and learning signals in the brain, such as those in the dopamine-rich striatum [2]. Indeed, much scientific evidence supports the hypothesis that the neural systems that balance immediate desires with long-term gains [3–5] function suboptimally in CCUs [6–8] and the very mechanisms evolved to protect are compromised in ways that drive addicts to choose cocaine. While this narrative organizes a wealth of experimental data, it also deemphasizes an important observation: not all decisions made by CCUs are unhealthy choices for drugs. For example, it has been demonstrated that cocaine users decrease cocaine self-administration when offered merchandise vouchers as an alternative to cocaine, with levels decreasing even further for direct money vouchers [9]. Furthermore, when cocaine users are
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