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Updated: May 21, 2026

Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice
Published on: March 11, 2020
The role of dopamine and glutamate modulation in Huntington disease
1Michael Trimble Neuropsychiatry Research Group, Department of Neuropsychiatry, BSMHFT and University of Birmingham, Birmingham, UK.
Background:
Huntington disease (HD) is an inherited neuropsychiatric condition with progressive neurodegenerative changes, mainly affecting the striatum. Pathological processes within the striatum are likely to lead to alterations in dopamine and glutamate activity in frontostriatal circuitry, resulting in characteristic motor, behavioural and cognitive symptoms.
Methods:
We conducted a systematic literature search in order to identify and review randomised, double-blinded, placebo-controlled trials of anti-dopaminergic and anti-glutamatergic therapy in HD.
Results:
Ten studies satisfied our selection criteria. These studies investigated a range of agents which act to antagonise dopamine (tetrabenazine, typical and atypical antipsychotics) or glutamate (amantadine, riluzole) transmission.
Discussion:
Although most agents showed efficacy in terms of amelioration of chorea, the available evidence did not allow us to identify a universally effective treatment. One difficulty associated with analysing the available evidence was a high prevalence of side effects, which prevented the full therapeutic potential of the medications from being adequately investigated. A further limitation is that many studies evaluated treatment effectiveness only in relation to patients' motor symptoms, even though behavioural and cognitive changes may negatively impact patients' quality of life. There is a clear need for further higher-level evidence addressing the effects of dopaminergic and glutamatergic agents on global functioning in HD.
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