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A Novel Translational Assay of Response Inhibition and Impulsivity: Effects of Prefrontal Cortex Lesions, Drugs Used in ADHD, and Serotonin 2C Receptor Antagonism

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Title
A Novel Translational Assay of Response Inhibition and Impulsivity: Effects of Prefrontal Cortex Lesions, Drugs Used in ADHD, and Serotonin 2C Receptor Antagonism
Published by
Nature Publishing Group, May 2013
DOI 10.1038/npp.2013.112
Pubmed ID
Authors

Trevor Humby, Jessica B Eddy, Mark A Good, Amy C Reichelt, Lawrence S Wilkinson

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-HT2C 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-HT2C receptor antagonism that suggest manipulation of 5-HT2C receptor function may be of use in correcting maladaptive impulsive behaviors and provide further evidence for dissociable contributions of serotonergic transmission to response control.

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Mendeley readers

The data shown below were compiled from readership statistics for 66 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 4 6%
Germany 2 3%
Portugal 1 2%
Japan 1 2%
Brazil 1 2%
Unknown 57 86%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 16 24%
Researcher 13 20%
Professor > Associate Professor 8 12%
Unspecified 7 11%
Student > Master 7 11%
Other 15 23%
Readers by discipline Count As %
Psychology 21 32%
Agricultural and Biological Sciences 15 23%
Neuroscience 12 18%
Unspecified 8 12%
Medicine and Dentistry 7 11%
Other 3 5%