title: Dissociable roles of dopamine and serotonin transporter function in a rat model of negative urgency.
abstract: Negative urgency is a facet of impulsivity that reflects mood-based rash action and is associated with various maladaptive behaviors in humans. However, the underlying neural mechanisms of negative urgency are not fully understood. Several brain regions within the mesocorticolimbic pathway, as well as the neurotransmitters dopamine (DA) and serotonin (5-HT), have been implicated in impulsivity. Extracellular DA and 5-HT concentrations are regulated by DA transporters (DAT) and 5-HT transporters (SERT); thus, these transporters may be important molecular mechanisms underlying individual differences in negative urgency. The current study employed a reward omission task to model negative urgency in rats. During reward trials, a cue light signaled the non-contingent delivery of one sucrose pellet; immediately following the non-contingent reward, rats responded on a lever to earn sucrose pellets (operant phase). Omission trials were similar to reward trials, except that non-contingent sucrose was omitted following the cue light prior to the operant phase. As expected, contingent responding was higher following omission of expected reward than following delivery of expected reward, thus reflecting negative urgency. Upon completion of behavioral training, Vmax and Km were obtained from kinetic analysis of [(3)H]DA and [(3)H]5-HT uptake using synaptosomes prepared from nucleus accumbens (NAc), dorsal striatum (Str), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC) isolated from individual rats. Vmax for DAT in NAc and for SERT in OFC were positively correlated with negative urgency scores. The current findings suggest that mood-based impulsivity (negative urgency) is associated with enhanced DAT function in NAc and SERT function in OFC.
authors.affiliation: Department of Psychological Science, Northern Kentucky University, Highland Heights, KY 41099, USA; Department of Psychology, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA; Center for Drug Abuse Research Translation, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Darna
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Cassandra D
authors.initials: CD
authors.lastname: Gipson
authors.affiliation: Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA; Center for Drug Abuse Research Translation, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Linda P
authors.initials: LP
authors.lastname: Dwoskin
authors.affiliation: Department of Psychology, University of Kentucky, Lexington, KY 40536, USA; Center for Drug Abuse Research Translation, University of Kentucky, Lexington, KY 40536, USA. Electronic address: mbardo@email.uky.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bardo
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003216:Conditioning, Operant / Q000502:physiology; D003463:Cues; D019422:Dietary Sucrose; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology*; D007175:Impulsive Behavior / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009483:Neuropsychological Tests; D016601:RNA-Binding Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012201:Reward; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*; D014316:Tritium
chemical_list: D019422:Dietary Sucrose; D050483:Dopamine Plasma Membrane Transport Proteins; D016601:RNA-Binding Proteins; C482440:Sert1 protein, rat; D014316:Tritium; D012701:Serotonin; D004298:Dopamine
keywords: Dopamine transporter; Negative urgency; Nucleus accumbens; Orbitofrontal cortex; Rat; Serotonin transporter