title: Contrasting effects of selective lesions of nucleus accumbens core or shell on inhibitory control and amphetamine-induced impulsive behaviour.
abstract: The core and shell subregions of the nucleus accumbens receive differential projections from areas of the medial prefrontal cortex that have dissociable effects on impulsive and perseverative responding. The contributions of these subregions to simple instrumental behaviour, inhibitory control and behavioural flexibility were investigated using a 'forced choice' task, various parameter manipulations and an omission schedule version of the task. Post-training, selective core lesions were achieved with microinjections of quinolinic acid and shell lesions with ibotenic acid. After a series of behavioural task manipulations, rats were re-stabilized on the standard version of the task and challenged with increasing doses of d-amphetamine (vehicle, 0.5 or 1.0 mg/kg i.p. 30 min prior to test). Neither core- nor shell-lesioned rats exhibited persistent deficits in simple instrumental behaviour or challenges to behavioural flexibility or inhibitory control. Significant differences between lesion groups were unmasked by d-amphetamine challenge in the standard version of the forced task. Core lesions potentiated and shell lesions attenuated the dose-dependent effect of d-amphetamine on increasing anticipatory responses seen in sham rats. These data imply that the accumbens core and shell subregions do not play major roles in highly-trained task performance or in challenges to behavioural control, but may have opposed effects following d-amphetamine treatment. Specifically, they suggest the shell subregion to be necessary for dopaminergic activation driving amphetamine-induced impulsive behaviour and the core subregion for the normal control of this behaviour via conditioned influences.
authors.affiliation: Behavioural and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Cambridge, UK. ermurphy@stanford.edu
authors.forename: E R
authors.initials: ER
authors.lastname: Murphy
authors.forename: E S J
authors.initials: ES
authors.lastname: Robinson
authors.forename: D E H
authors.initials: DE
authors.lastname: Theobald
authors.forename: J W
authors.initials: JW
authors.lastname: Dalley
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D002755:Choice Behavior / Q000187:drug effects; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000494:pharmacology; D007175:Impulsive Behavior; D007266:Inhibition, Psychological; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects
chemical_list: D018765:Dopamine Uptake Inhibitors; D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid; D017378:Quinolinic Acid; D003913:Dextroamphetamine; D004298:Dopamine