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Neurosci Lett. 2015 May 19;595:50-3. doi: 10.1016/j.neulet.2015.03.067. Epub 2015 Apr 1.

Histidine decarboxylase knockout mice, a genetic model of Tourette syndrome, show repetitive grooming after induced fear.

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Department of Psychiatry, Yale Univeristy, New Haven, CT, USA.
Tohoku University, Graduate School of Engineering, Sendai, Japan.
Department of Psychiatry, Yale Univeristy, New Haven, CT, USA; Department of Psychology, Yale Univeristy, New Haven, CT, USA; Child Study Center, Yale Univeristy, New Haven, CT, USA; Interdepartmental Neuroscience Program, Yale Univeristy, New Haven, CT, USA. Electronic address:


Tics, such as are seen in Tourette syndrome (TS), are common and can cause profound morbidity, but they are poorly understood. Tics are potentiated by psychostimulants, stress, and sleep deprivation. Mutations in the gene histidine decarboxylase (Hdc) have been implicated as a rare genetic cause of TS, and Hdc knockout mice have been validated as a genetic model that recapitulates phenomenological and pathophysiological aspects of the disorder. Tic-like stereotypies in this model have not been observed at baseline but emerge after acute challenge with the psychostimulant d-amphetamine. We tested the ability of an acute stressor to stimulate stereotypies in this model, using tone fear conditioning. Hdc knockout mice acquired conditioned fear normally, as manifested by freezing during the presentation of a tone 48h after it had been paired with a shock. During the 30min following tone presentation, knockout mice showed increased grooming. Heterozygotes exhibited normal freezing and intermediate grooming. These data validate a new paradigm for the examination of tic-like stereotypies in animals without pharmacological challenge and enhance the face validity of the Hdc knockout mouse as a pathophysiologically grounded model of tic disorders.


Histamine; Histidine decarboxylase; Stereotypical behavior; Stress; Tics; Tourette syndrome

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