• Ronald Keiflin, Rebecca M Reese, Catherine A Woods, and Patricia H Janak.
• Ernest Gallo Clinic and Research Center, Department of Neurology, Wheeler Center for the Neurobiology of Addiction, University of California at San Francisco, San Francisco, California 94143.
• J. Neurosci. 2013 Oct 2; 33 (40): 15989-98.

AbstractAnimals rely on environmental cues to identify potential rewards and select the best reward available. The orbitofrontal cortex (OFC) is proposed to encode sensory-specific representations of expected outcome. However, its contribution to the selection of a preferred outcome among different reward options is still unclear. We investigated the effect of transient OFC inactivation (achieved by presession injection of muscimol and baclofen) in a novel two-reward choice task. In discrete trials, rats could choose between a solution of polycose and an equally caloric, but highly preferred, solution of sucrose by visiting one of two liquid dispensers after the presentation of a specific cue signaling the availability of one or both of the solutions. We found that OFC inactivation did not affect outcome preference: rats maintained high preference for sucrose and adapted their behavioral responding when the cue-outcome contingencies were reversed. However, when rats were tested drug-free 24 h after OFC inactivation and reversal learning, memory for the newly learned contingencies was poor. These results suggest a potential conflict between OFC (encoding pre-reversal contingencies) and other brain circuits (encoding the new contingencies). Remarkably, repeating the OFC inactivation before the reversal memory test restored normal behavior, confirming the hypothesis of a dominant impact of OFC on other decision-making circuits. These results indicate that the representations encoded in the OFC, while not essential to the expression of outcome preference, exert hierarchical control on downstream decision-making circuits.

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