A novel translational assay of response inhibition and impulsivity: Effects of prefrontal cortex lesions, drugs used in ADHD, and serotonin 2C receptor antagonism

Humby, T, Eddy, J, Good, M, Reichelt, A and Wilkinson, L 2013, 'A novel translational assay of response inhibition and impulsivity: Effects of prefrontal cortex lesions, drugs used in ADHD, and serotonin 2C receptor antagonism', Neuropsychopharmacology, vol. 38, no. 11, pp. 2150-2159.


Document type: Journal Article
Collection: Journal Articles

Title A novel translational assay of response inhibition and impulsivity: Effects of prefrontal cortex lesions, drugs used in ADHD, and serotonin 2C receptor antagonism
Author(s) Humby, T
Eddy, J
Good, M
Reichelt, A
Wilkinson, L
Year 2013
Journal name Neuropsychopharmacology
Volume number 38
Issue number 11
Start page 2150
End page 2159
Total pages 10
Publisher Nature
Abstract Animal models are making an increasing contribution to our understanding of the psychology and brain mechanisms underlying behavioral inhibition and impulsivity. The aim here was to develop, for the first time, a mouse analog of the stop-signal reaction time task with high translational validity in order to be able to exploit this species in genetic and molecular investigations of impulsive behaviors. Cohorts of mice were trained to nose-poke to presentations of visual stimuli. Control of responding was manipulated by altering the onset of an auditory 'stop-signal' during the go response. The anticipated systematic changes in action cancellation were observed as stopping was made more difficult by placing the stop-signal closer to the execution of the action. Excitotoxic lesions of medial prefrontal cortex resulted in impaired stopping, while the clinically effective drugs methylphenidate and atomoxetine enhanced stopping abilities. The specific 5-HT 2C receptor antagonist SB242084 also led to enhanced response control in this task. We conclude that stop-signal reaction time task performance can be successfully modeled in mice and is sensitive to prefrontal cortex dysfunction and drug treatments in a qualitatively similar manner to humans and previous rat models. Additionally, using this model we show novel and highly discrete effects of 5-HT 2C receptor antagonism that suggest manipulation of 5-HT 2C receptor function may be of use in correcting maladaptive impulsive behaviors and provide further evidence for dissociable contributions of serotonergic transmission to response control. © 2013 American College of Neuropsychopharmacology. All rights reserved.
Subject Central Nervous System
Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Keyword(s) 5-HT receptor antagonism 2C
ADHD
Mouse models
Stop-signal reaction time task
Translation
DOI - identifier 10.1038/npp.2013.112
Copyright notice © 2013 American College of Neuropsychopharmacology. All rights reserved.
ISSN 0893-133X
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