title: Role of medial prefrontal and orbitofrontal monoamine transporters and receptors in performance in an adjusting delay discounting procedure.
abstract: Performance in an adjusting delay discounting procedure is predictive of drug abuse vulnerability; however, the shared underlying specific prefrontal neural systems linking delay discounting and increased addiction-like behaviors are unclear. Rats received direct infusions of methylphenidate (MPH; 6.25, 25.0, or 100μg), amphetamine (AMPH; 0.25, 1.0, or 4.0μg), or atomoxetine (ATO; 1.0, 4.0, or 16.0μg) into either medial prefrontal cortex (mPFC) or orbitofrontal cortex (OFC) immediately prior to performance in an adjusting delay task. These drugs were examined because they are efficacious in treating impulse control disorders. Because dopamine (DA) and serotonin (5-HT) receptors are implicated in impulsive behavior, separate groups of rats received microinfusions of the DA receptor-selective drugs SKF 81297 (0.1 or 0.4µg), SCH 23390 (0.25 or 1.0µg), quinpirole (1.25 or 5.0µg), and eticlopride (0.25 or 1.0µg), or received microinfusions of the 5-HT receptor-selective drugs 8-OH-DPAT (0.025 or 0.1μg), WAY 100635 (0.01 or 0.04μg), DOI (2.5 or 10.0μg), and ketanserin (0.1 or 0.4μg). Impulsive choice was not altered significantly by MPH, AMPH, or ATO into either mPFC or OFC, indicating that neither of these prefrontal regions alone may mediate the systemic effect of ADHD medications on impulsive choice. However, quinpriole (1.25μg) and eticlopride infused into mPFC increased impulsive choice, whereas 8-OH-DPAT infused into OFC decreased impulsive choice. These latter results demonstrate that blockade of DA D2 receptors in mPFC or activation of 5-HT1A receptors in OFC increases impulsive choice in the adjusting delay procedure.
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.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Psychology, Kalamazoo College, Kalamazoo, MI 49006, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Perry
authors.affiliation: Department of Psychiatry, University of Vermont, Burlington VT 05401, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Meyer
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 Biostatistics, University of Kentucky, Lexington, KY 40506, USA; Center for Drug Abuse Research Translation, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Charnigo
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: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D016739:Behavior, Addictive / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D065786:Delay Discounting / Q000187:drug effects / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011437:Propylamines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D011437:Propylamines; D017448:Receptors, Dopamine D2; D018490:Serotonin Agents; D050493:Vesicular Monoamine Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D000661:Amphetamine
keywords: Adjusting delay discounting; Dopamine receptor; Dopamine transporter; Norepinephrine transporter; Rat; Serotonin receptor