title: Gamma aminobutyric acidergic and neuronal structural markers in the nucleus accumbens core underlie trait-like impulsive behavior.
abstract: BACKGROUND
  Pathological forms of impulsivity are manifest in a number of psychiatric disorders listed in DSM-5, including attention-deficit/hyperactivity disorder and substance use disorder. However, the molecular and cellular substrates of impulsivity are poorly understood. Here, we investigated a specific form of motor impulsivity in rats, namely premature responding, on a five-choice serial reaction time task.
  
  
  METHODS
  We used in vivo voxel-based magnetic resonance imaging and ex vivo Western blot analyses to investigate putative structural, neuronal, and glial protein markers in low-impulsive (LI) and high-impulsive rats. We also investigated whether messenger RNA interference targeting glutamate decarboxylase 65/67 (GAD65/67) gene expression in the nucleus accumbens core (NAcbC) is sufficient to increase impulsivity in LI rats.
  
  
  RESULTS
  We identified structural and molecular abnormalities in the NAcbC associated with motor impulsivity in rats. We report a reduction in gray matter density in the left NAcbC of high-impulsive rats, with corresponding reductions in this region of glutamate decarboxylase (GAD65/67) and markers of dendritic spines and microtubules. We further demonstrate that the experimental reduction of de novo of GAD65/67 expression bilaterally in the NAcbC is sufficient to increase impulsivity in LI rats.
  
  
  CONCLUSIONS
  These results reveal a novel mechanism of impulsivity in rats involving gamma aminobutyric acidergic and structural abnormalities in the NAcbC with potential relevance to the etiology and treatment of attention-deficit/hyperactivity disorder and related disorders.
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom. Electronic address: daniele.caprioli@nih.gov.
authors: Daniele
authors: D
authors: Caprioli
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Stephen J
authors: SJ
authors: Sawiak
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Emiliano
authors: E
authors: Merlo
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: David E H
authors: DE
authors: Theobald
authors: Division Neurobiology of Behaviour, Department of Animals in Science and Society, Utrecht University, Utrecht, The Netherlands.
authors: Marcia
authors: M
authors: Spoelder
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Bianca
authors: B
authors: Jupp
authors: Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, United Kingdom.
authors: Valerie
authors: V
authors: Voon
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: T Adrian
authors: TA
authors: Carpenter
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Barry J
authors: BJ
authors: Everitt
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Trevor W
authors: TW
authors: Robbins
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Jeffrey W
authors: JW
authors: Dalley
mesh_terms: D000818:Animals; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D007839:Functional Laterality; D015870:Gene Expression / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000096:biosynthesis*; D007175:Impulsive Behavior / Q000378:metabolism* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008870:Microtubules / Q000378:metabolism*; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology*; D059906:Neuroimaging; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D051381:Rats
chemical_list: D015415:Biomarkers; D020319:Oligodeoxyribonucleotides, Antisense; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: Attention-deficit/hyperactivity disorder; GABA; impulsivity; magnetic resonance imaging; nucleus accumbens; psychostimulants
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