The orbitofrontal cortex (OFC) and basolateral amygdala (BLA) are critical for using learned representations of outcomes to guide behavior. Neurophysiological findings suggest complementary roles in which the BLA acquires associations between cues and outcomes and the OFC subsequently uses them to guide behavior. Here, we have used a reinforcer devaluation paradigm to test this hypothesis. In this paradigm, rats are first trained to associate a light conditioned stimulus (CS) with a food outcome, and then the food is devalued by pairing it with illness. After this devaluation procedure, responding to the CS is assessed in a single probe session. Previously, we have shown that BLA and OFC lesions made before training do not affect the acquisition of conditioned responding but do impair the sensitivity of that responding to reinforcer devaluation. Rats with such lesions fail to exhibit the spontaneous decrease in conditioned responding to the light cue observed in controls in the probe test. Here, we have extended those findings by showing that performance in the probe test is impaired by OFC lesions made after light-food conditioning but not by BLA lesions made after that training. These findings indicate that the OFC and BLA play different roles in mediating normal goal-directed performance in this, and likely other, settings. The BLA seems critical to forming representations linking cues to the incentive properties of outcomes but not for maintaining these representations in memory, updating them with new information, or for expressing them in behavior. In contrast, the OFC seems essential for one or more of these latter processes.

Significance: Alcoholism is characterized by a progressive degradation of executive control and an increase in compulsive alcohol seeking that is hypothesized to involve a shift from prefrontal cortex to dorsal striatal (DLS) control over behavior. Here, we show that mice exposed to chronic intermittent alcohol exhibited expansion of dendritic material in DLS neurons, coupled with loss of endocannabinoid CB1 receptor signaling and CB1-mediated long-term depression in the DLS. Behaviorally, chronic alcohol exposure facilitated various forms of DLS-dependent learning and augmented in vivo DLS neuronal activity as correct learned choices were made. These findings support a model in which chronic ethanol causes DLS neuroadaptations that prime for greater striatal control over behavior, potentially contributing to the progression of alcoholism.

The orbitofrontal cortex (OFC) has been implicated in the use of outcome expectancies to guide behavior. The present study used a devaluation task to examine this function. Rats first received light-food pairings followed by food-toxin pairings designed to devalue the food. After either excitotoxic or sham OFC lesions, responding to the light was reassessed. Sham-lesioned rats showed reduced responding to the light relative to behavioral controls, which had received food and toxin unpaired. In contrast, OFC-lesioned rats showed no such reductions. Combined with previous data (C. L. Pickens, M. P. Saddoris, B. Setlow, M. Gallagher, P. C. Holland, & G. Schoenbaum, 2003), these results indicate that the OFC is critical for the maintenance of information about the current incentive value of reinforcers or the use of that information to guide behavior.