title: Prefrontal cortical-striatal dopamine receptor mRNA expression predicts distinct forms of impulsivity.
abstract: Variation in dopamine receptor levels has been associated with different facets of impulsivity. To further delineate the neural substrates underlying impulsive action (inability to withhold a prepotent motor response) and impulsive choice (delay aversion), we characterised rats in the Differential Reinforcement of Low Rates of Responding task and a delay discounting task. We also measured performance on an effort-based discounting task. We then assessed D1 and D2 dopamine receptor mRNA expression in subregions of the prefrontal cortex and nucleus accumbens using in situ hybridisation, and compared these data with behavioral performance. Expression of D1 and D2 receptor mRNA in distinct brain regions was predictive of impulsive action. A dissociation within the nucleus accumbens was observed between subregions and receptor subtypes; higher D1 mRNA expression in the shell predicted greater impulsive action, whereas lower D2 mRNA expression in the core predicted greater impulsive action. We also observed a negative correlation between impulsive action and D2 mRNA expression in the prelimbic cortex. Interestingly, a similar relationship was present between impulsive choice and prelimbic cortex D2 mRNA, despite the fact that behavioral indices of impulsive action and impulsive choice were uncorrelated. Finally, we found that both high D1 mRNA expression in the insular cortex and low D2 mRNA expression in the infralimbic cortex were associated with willingness to exert effort for rewards. Notably, dopamine receptor mRNA in these regions was not associated with either facet of impulsivity. The data presented here provide novel molecular and neuroanatomical distinctions between different forms of impulsivity, as well as effort-based decision-making.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA. nws7@pitt.edu
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Simon
authors.forename: Blanca S
authors.initials: BS
authors.lastname: Beas
authors.forename: Karienn S
authors.initials: KS
authors.lastname: Montgomery
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Haberman
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bizon
authors.forename: Barry
authors.initials: B
authors.lastname: Setlow
mesh_terms: D000818:Animals; D002755:Choice Behavior; D007175:Impulsive Behavior / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity; D017397:Prefrontal Cortex / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D012054:Reinforcement, Psychology; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2