title: Deficits in impulse control associated with tonically-elevated serotonergic function in rat prefrontal cortex.
abstract: 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.
authors: Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. jwd20@cus.cam.ac.uk
authors: Jeffrey W
authors: JW
authors: Dalley
authors: David E
authors: DE
authors: Theobald
authors: Dawn M
authors: DM
authors: Eagle
authors: F
authors: F
authors: Passetti
authors: Trevor W
authors: TW
authors: Robbins
mesh_terms: D000818:Animals; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000378:metabolism / Q000523:psychology; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D007175:Impulsive Behavior / Q000378:metabolism* / Q000523:psychology; D008297:Male; D017397:Prefrontal Cortex / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D012701:Serotonin / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D012701:Serotonin; D004298:Dopamine