Once addiction has developed, decreased ability to avoid drug craving and/or inhibit drug-seeking behavior commonly manifests despite decreased hedonic effects of the drug. These inhibitory ‘top-down’ deficits may emerge from a lack of executive control over circuits that parse reward/saliency, aversion avoidance/stress reactivity, interoception, and motivation (Koob & Le Moal, 2001; Volkow, Fowler, & Wang, 2003; Volkow, et al., 2011). Decreased hedonic drug effects may stem from a shift away from phasic and tonic midbrain dopamine firing patterns toward more tonic firing, which results in lower levels of dopamine release (Grace, 2000). Blunted dopamine release and decreased hedonic effects have been observed in cocaine-addicted individuals challenged with either methylphenidate (a cocaine-like compound) or amphetamine (Martinez et al., 2007; Volkow et al., 1997; Volkow, et al., 2011). These and other neural adaptations induced by the drug are thought to usurp normal learning and habit circuitry and increasingly recruit cortical glutamatergic signalling (Bowers, Chen, & Bonci, 2010; Kalivas, 2009; Kalivas & O’Brien, 2008b; Koob & Volkow, 2010; Luscher & Malenka, 2011), which can manifest as compulsive drug-seeking behavior and relapse (Everitt & Wolf, 2002; Hyman, Malenka, & Nestler, 2006).
