title: Impulsive action and impulsive choice are mediated by distinct neuropharmacological substrates in rat.
abstract: Impulsivity is a heterogeneous construct according to clinical and preclinical behavioural measures and there is some preliminary evidence indicating distinct neurobiological substrates underlying the sub-components of impulsivity. Two preclinical assays, the five-choice serial reaction time task (5-CSRTT) and the delayed discounting task (DDT), are hypothesized to provide measures of impulsive action (premature responding) and impulsive choice (percent choice for delayed reward), respectively. In the present studies, we show that the norepinephrine reuptake inhibitor atomoxetine attenuated premature responding in the 5-CSRTT, but was ineffective in the DDT. The mixed dopamine/norepinephrine reuptake inhibitor methylphenidate exhibited an opposite profile of effects. In addition, blockade of 5-HT2A/C receptors via ketanserin decreased premature responding but had no effects on percent choice for delayed reward; blockade of 5-HT2C receptors via SB 242084 had opposite effects. Follow-up studies provided some limited evidence of additive effects of 5-HT2A/C receptor blockade on the effects of atomoxetine on impulsive action. These studies demonstrate dissociable profiles of stimulant vs. non-stimulant attention deficit hyperactivity disorder medications and 5-HT subtype-selective ligands, in the 5-CSRTT and DDT assays. Thus, the present findings support the sub-categorization of impulsivity and suggest that 5-HT receptor subtype-selective antagonists may provide therapeutic targets for disorders characterized by different forms of impulsivity.
authors.affiliation: PsychoGenics Inc., 765 Old Saw Mill River Road, Tarrytown, NY 10591, USA. Neil.Paterson@PsychoGenics.com
authors.forename: Neil E
authors.initials: NE
authors.lastname: Paterson
authors.forename: Caitlin
authors.initials: C
authors.lastname: Wetzler
authors.forename: Adrian
authors.initials: A
authors.lastname: Hackett
authors.forename: Taleen
authors.initials: T
authors.lastname: Hanania
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007175:Impulsive Behavior / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007650:Ketanserin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use; D011437:Propylamines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D018759:Adrenergic Uptake Inhibitors; D000631:Aminopyridines; D018765:Dopamine Uptake Inhibitors; D007211:Indoles; D011437:Propylamines; D058830:Serotonin 5-HT2 Receptor Antagonists; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D007650:Ketanserin