title: The synergy of working memory and inhibitory control: behavioral, pharmacological and neural functional evidences.
abstract: Concomitant deficits in working memory and behavioral inhibition in several psychiatric disorders like attention-deficit/hyperactivity disorder, addiction or mania, suggest that common brain mechanisms may underlie their etiologies. Based on the theoretical assumption that a continuum exists between health and mental disorders, we explored the relationship between working memory and inhibition in healthy individuals, through spontaneous inter individual differences in behavior, and tested the hypothesis of a functional link through the fronto-striatal dopaminergic system. Rats were classified into three groups, showing good, intermediate and poor working memory and were compared for their inhibitory abilities. These two functions were simultaneously modulated by a dose-effect of d-amphetamine and in situ hybridization was used to quantify dopaminergic receptor (RD1) mRNAs in prefrontal cortex and striatal areas. A functional relationship between working memory and inhibition abilities was revealed. Both functions were similarly modulated by d-amphetamine according to an inverted-U shaped relationship and depending on initial individual performances. D-amphetamine selectively improved working memory and inhibition of poor and intermediate performers at low doses whereas it impaired both processes in good performers at a higher dose. D1 receptors were less expressed in prelimbic, infralimbic and anterior cingulate cortices of good compared to intermediate and poor performers, whereas no difference was observed between groups in striatal areas. The synergy of working memory and inhibitory abilities, observed in both healthy and psychiatric populations, may originate from endogenous variability in dopaminergic prefrontal cortex activity. Such findings confirm the validity of a dimensional approach, based on the concept of continuity between health and mental disorders for identifying endophenotypes of mental disorders.
authors.affiliation: CNRS, INCIA, UMR 5287, F-33000 Bordeaux, France; Univ. Bordeaux, INCIA, UMR 5287, F-33000 Bordeaux, France. stephanie.gregoire.sg@gmail.com
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Grégoire
authors.forename: Marion
authors.initials: M
authors.lastname: Rivalan
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Moine
authors.forename: Françoise
authors.initials: F
authors.lastname: Dellu-Hagedorn
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D007266:Inhibition, Psychological; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D003913:Dextroamphetamine