title: Prefrontal cortical neuregulin-ErbB modulation of inhibitory control in rats.
abstract: Impulse control disturbances are key features of various neuropsychiatric and neurological disorders, such as attention-deficit/hyperactivity disorder, drug addiction, Parkinson disease and schizophrenia. Whereas over the last years accumulating evidence has highlighted monoaminergic modulation of the processes underlying impulse control, investigating novel mechanisms beyond monoamines may provide new intervention strategies to ameliorate impulse control disturbances. Recent work has associated the neuregulin (Nrg)-ErbB pathway with several neuropsychiatric diseases, as well as indicated its involvement in murine measures of impulse control. The aim of the present study was to investigate whether this Nrg-ErbB signaling pathway also modulates impulsive action in rats. To this end, a group of rats was trained in the 5-choice serial reaction time task (5-CSRTT), an operant paradigm that provides measures of visuospatial attention and inhibitory control processes. Upon stable baseline performance, the ErbB tyrosine kinase receptor inhibitor JNJ-28871063 (JNJ) was intracranially infused into the medioprefrontal cortex prior to test sessions. Results showed that JNJ dose-dependently improved measures of impulsive action. Importantly, other measures in the 5-CSRTT reflecting visuospatial attention or aspects of motivational behavior were not altered by JNJ. In conclusion, the present data strengthen a role for the Nrg-ErbB4 pathway in the prefrontal cortex in cognitive functioning, and in particular point towards involvement in the processes underlying impulse control.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Neuroscience Campus Amsterdam, Center for Neurogenomic and Cognitive Research, VU University, Amsterdam, The Netherlands; Sylics (Synaptologics BV), Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Loos
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dustin
authors.initials: D
authors.lastname: Schetters
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Myrthe
authors.initials: M
authors.lastname: Hoogeland
authors.affiliation: Department of Molecular and Cellular Neurobiology, Neuroscience Campus Amsterdam, Center for Neurogenomic and Cognitive Research, VU University, Amsterdam, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Spijker
authors.affiliation: Department of Molecular and Cellular Neurobiology, Neuroscience Campus Amsterdam, Center for Neurogenomic and Cognitive Research, VU University, Amsterdam, The Netherlands; Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Taco J
authors.initials: TJ
authors.lastname: de Vries
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: t.pattij@vumc.nl.
authors.forename: Tommy
authors.initials: T
authors.lastname: Pattij
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007175:Impulsive Behavior / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D020880:Neuregulins / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects
chemical_list: C526582:JNJ 28871063; D009025:Morpholines; D020880:Neuregulins; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D066246:ErbB Receptors
keywords: Cognition; ErbB4; Impulsivity; Neuregulin; Prelimbic cortex; Rat