title: Effects of selective dopaminergic compounds on a delay-discounting task.
abstract: Impulsivity is widely regarded as a multidimensional trait that encompasses two or more distinct patterns of behavior, and dopaminergic systems are implicated in the expression of impulsive behavior in both humans and animal subjects. Impulsive choice, or the tendency to choose rewards associated with relatively little or no delay, has been extensively studied in humans and animal subjects using delay-discounting tasks. Here, delay-discounting procedures were used to assess the effects of receptor-selective dopaminergic agonists, antagonists, and dopamine transporter ligands on choices of immediate versus delayed sucrose pellets. The effects of d-amphetamine, GBR 12909, apomorphine, SKF 81297, sumanirole, pramipexole, ABT-724, SCH 23390, L-741,626, PG01037, and L-745,870 were assessed in 24 Sprague-Dawley rats. The only drugs to affect impulsive choice selectively without altering undelayed choice were the D1-like antagonist, SCH 23390 (0.01 mg/kg), and the D4 partial agonist, ABT-724 (3.2 mg/kg), which both increased impulsive choice. The shared effects of these compounds may be explained by their localization within the prefrontal cortex on different groups of neurons. None of the selective agonists and antagonists tested reduced impulsive choice, so further research is needed to determine if direct dopaminergic agonists or antagonists may be therapeutically useful in the treatment of impulse-control disorders.
authors.affiliation: Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA. mkoffar1@jhmi.edu
authors.forename: Mikhail N
authors.initials: MN
authors.lastname: Koffarnus
authors.forename: Amy H
authors.initials: AH
authors.lastname: Newman
authors.forename: Peter
authors.initials: P
authors.lastname: Grundt
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.forename: James H
authors.initials: JH
authors.lastname: Woods
mesh_terms: D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D003627:Data Interpretation, Statistical; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior / Q000523:psychology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors; D050638:Receptors, Dopamine D4 / Q000819:agonists / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule
chemical_list: D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D017447:Receptors, Dopamine D1; D050638:Receptors, Dopamine D4