Morgado et al. Stress affects pavlovian-to-instrumental transfer FIGURE 2 | Instrumental conditioning. Both experimental groups acquired the lever pressing task and were able to correctly distinguish devalued from valued levers.*p < 0.05. FIGURE 3 | Stress-induced impairment of Pavlovian-to-instrumental transfer is reversible. Stress exposure resulted in an impairment of the association between Pavlovian and instrumental behavior (A), which was no longer observed after a 6-week period without exposure to stressful stimuli (B). Same – conditioned stimulus (sound) predicted the same outcome as the lever pressed; Diff – conditioned stimulus (sound) predicted a different outcome as the lever pressed. *p < 0.05. present protocol), stressed animals were still able to effectively sup- press the devaluated response, which was not the case when the test was performed later during training (Dias-Ferreira et al., 2009). Since neither Pavlovian conditioning nor instrumental learning are affected by chronic stress, the most likely explanation for the herein observed stress-induced impairment of PIT seems to be a deﬁcit in the transfer between the two networks. The precise neu- ronal networks implicated in PIT are still being described. As stated before, several regions that are known to be susceptible to chronic stress are crucial to PIT. In fact, several studies demonstrate that the mPFC and OFC encode distinct components of both Pavlov- ian and instrumental processes (Gallagher et al., 1999; Chudasama and Robbins, 2003; Ostlund and Balleine, 2007; Homayoun and Moghaddam, 2008) and a recent study reveals that the OFC and mPFC orchestrate the integration of Pavlovian and instrumental processes during PIT (Homayoun and Moghaddam, 2009). This integration involves distinct operations as mPFC and OFC display predominantly inhibitory and excitatory phasic responses to the same events, respectively. Taken into account our previous obser- vations that stress triggers atrophy in the mPFC and hypertrophy in the OFC (Dias-Ferreira et al., 2009), we suggest the existence of an imbalance in these inhibitory/excitatory responses and, as a consequence, a failure in the reinforcement of goal-directed actions by conditioned stimuli. Frontiers in Neuroscience | Decision Neuroscience June 2012 | Volume 6 | Article 93 | 4