ArticleThe international journal of neuropsychopharmacology2025
Frequent vocalizations and deep brain stimulation-responsive hyperkinesia in a striatal disinhibition rat model for Tourette syndrome.
Article in The international journal of neuropsychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- A Celsr3 Mutation Linked to Tourette Disorder Disrupts Cortical Dendritic Patterning and Striatal Cholinergic Interneuron Excitability.International journal of molecular sciences · 2025Article
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Abstract
backgroundThe lack of a rodent model for both motor and phonic tics hinders research on deep brain stimulation (DBS) for refractory Tourette syndrome (TS). Striatal disinhibition with a gamma-aminobutyric acid A antagonist (bicuculline) was previously shown to induce hyperkinesia and vocalizations in monkeys, indicating its potential as a TS model. In rats, however, only hyperkinesia was validated, prompting us to investigate whether they can also develop abnormal vocalizations and whether both conditions respond to thalamic DBS.
methodsRats underwent surgical implantation of a unilateral guide cannula targeting the caudate putamen (CPu) or nucleus accumbens (NAc). Additionally, they were implanted with an ipsilateral stimulation electrode targeting the border between the central medial (CM) and ventrolateral (VL) thalamic nuclei. Motor changes and ultrasound vocalizations were recorded and characterized offline.
resultsCPu bicuculline elicited arrhythmic shoulder jerks that tend to appear in fading bursts and sporadically alternate with sustained generalized hyperextension. Nucleus accumbens bicuculline elicited similar hyperkinesia, but at a much lower dose to prevent convulsions. DBS of CM/VL, but not adjacent regions, attenuated hyperkinesia with lower intensity showing stronger effects. In addition, bicuculline in NAc, but not CPu, elicited nonsensical vocalizations. However, the effect of CM/VL DBS on vocalizations remained inconclusive.
conclusionsHyperkinesia temporal features, co-development with vocalizations, and responsiveness to CM/VL DBS suggest striatal disinhibition may serve as a TS rat model. However, other movement disorders with vocal complications cannot be excluded, given the challenge of validating key tic indicators in animals, such as premonitory urge and suppressibility.
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