In behavioral studies, poor performance on such tasks is supposed to reflect the inability of drug-addicted individuals to learn new healthy behaviors and avoid the negative consequences of their drug consumption. Such learning and/or changes in behavior require signals from the frontal cortex to indicate the value of decisions. Studies found that binge drinking induces persistent deficits in reversal learning in rats (Obernier et al. 2002; Pascual et al. 2007) and in adult mice following a model of adolescent binge drinking (Coleman 2010). Other investigators similarly have demonstrated that cocaine use results in abnormally slow reversal learning, even though initial learning is normal (Calu et al. 2007; Schoenbaum et al. 2004). Specifically, human cocaine and alcohol addicts exhibit dysfunctional decision making in reversal-learning tasks that probe cognitive flexibility (Bechara et al. 2002). Lesions in the frontal cortex cause reversal-learning deficits comparable to those induced by chronic drug abuse (Schoenbaum et al. 2006). The persistence of addiction matches the persistent increases in innate immune gene activation (Qin et al. 2007, 2008) and loss of behavioral flexibility. Thus, it is thought that innate immune gene induction in the frontal cortex disrupts decision making consistent with addiction (Crews et al. 2011).
