Tiagabine treatment in kainic acid induced cerebellar lesion of dystonia rat model
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Date
2016-11-17
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Abstract
Dystonia is a neurological disorder characterized by excessive involuntary muscle contractions
that lead to twisting movements. The exaggerated movements have been studied and
have implicated basal ganglia as the point of origin. In more recent studies, the cerebellum has
also been identified as the possible target of dystonia, in the search for alternative treatments.
Tiagabine is a selective GABA transporter inhibitor, which blocks the reuptake and recycling
of GABA. The study of GABAergic drugs as an alternative treatment for cerebellar induced
dystonia has not been reported. In our study, tiagabine was i.p. injected into kainic acid induced,
cerebellar dystonic adult rats, and the effects were compared with non-tiagabine injected
and sham-operated groups. Beam walking apparatus, telemetric electromyography
(EMG) recording, and histological verification were performed to confirm dystonic symptoms
in the rats on post-surgery treatment. Involuntary dystonic spasm was observed with repetitive
rigidity, and twisting movements in the rats were also confirmed by a high score on the dystonic
scoring and a high amplitude on the EMG data. The rats with tiagabine treatment were
scored based on motor amelioration assessed via beam walking. The result of this study suggests
and confirms that low dose of kainic acid microinjection is sufficient to induce dystonia
from the cerebellar vermis. In addition, from the results of the EMG recording and the behavioral
assessment through beam walking, tiagabine is demonstrated as being effective in reducing
dystonic spasm and may be a possible alternative therapeutic drug in the treatment of dystonia.
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Keywords
dystonia, cerebellum, kainic acid, tiagabine, telemetry recording