Double Dissociation between Serotonergic and Dopaminergic Modulation of Medial Prefrontal and Orbitofrontal Cortex during a Test of Impulsive Choice

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Abstract
Dysregulation of the prefrontal cortex (PFC) has been implicated in impulse control disorders, including attention deficit hyperactivity disorder. A growing body of evidence suggests that impulsivity is non-unitary in nature, and recent data indicate that the ventral and dorsal regions of the PFC are differentially involved in distinct aspects of impulsive behaviour, findings which may reflect differences in the monoaminergic regulation of these regions. In the current experiment, levels of dopamine, serotonin and their metabolites were measured in the medial PFC (n = 12) and orbitofrontal cortex (OFC) (n = 19) of rats using in vivo microdialysis during the delay-discounting model of impulsive choice, where impulsivity is defined as selection of small immediate over larger delayed rewards. Yoked groups were also dialysed to control for instrumental responding and reward delivery. Significant increases in 5-hydroxytryptamine efflux were observed in the mPFC, but not in the OFC, during task performance but not under yoked control conditions. In the OFC, 3,4-di-hydroxy-phenylocetic acid (DOPAC) levels increased in animals performing the task but not in yoked animals, whereas mPFC DOPAC levels increased in all subjects. These data suggest a double dissociation between serotonergic and dopaminergic modulation of impulsive decision-making within distinct areas of frontal cortex.