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Converging lines of evidence suggest that dysfunction of brain serotonergic systems may underlie impulsive behavior. However, the nature of this deficit remains poorly understood because indirect indices of serotonin (5-HT) function are often used in clinical and experimental studies. In this investigation we measured 5-HT release directly in the prefrontal cortex of rats using in vivo microdialysis during performance of a visual attentional task. A number of performance measures were taken, including the number of premature responses made during the inter-trial interval before the onset of the visual discriminanda. This form of behavioral disinhibition was defined as impulsive, after. Lengthening the inter-trial interval increased the sensitivity of the task for detecting impulsive tendencies. Cortical levels of 5-HT and its metabolite 5-HIAA remained at pre-task levels over 1 h of task performance. By contrast, levels of dopamine (DA) and its metabolite DOPAC increased during this period. Regression analysis established a positive relationship between premature (impulsive) responses and 5-HT efflux, both under basal (r = 0.49) and task-related (r = 0.42) conditions (n = 31). No such relationship was found for prefrontal levels of DA. However, post-mortem analysis revealed that animals that were more impulsive had a higher turnover of DA in anterior cingulate, prelimbic and infralimbic cortices but no detectable abnormalities in 5-HT function. These data indicate that elevated 5-HT release in the prefrontal cortex may underlie deficits in impulse control on this task. Additionally, DA dysfunction in this region may be another, possibly independent, trait marker of impulsivity.

Deficits in Impulse Control Associated with Tonically-elevated Serotonergic Function in Rat Prefrontal Cortex