Assini, Robert. Extrastriatal GABAA receptors as a nondopaminergic target in the treatment of motor symptoms of Parkinson's disease and levodopa-induced dyskinesia. Retrieved from https://doi.org/doi:10.7282/t3-q4gd-vx26
TitleExtrastriatal GABAA receptors as a nondopaminergic target in the treatment of motor symptoms of Parkinson's disease and levodopa-induced dyskinesia
DescriptionParkinson’s disease is a progressive neurodegenerative disorder resulting from the death of the dopaminergic nigrostriatal projection to the basal ganglia. Extrastriatal nuclei within this circuit have been shown to exhibit synchronous oscillatory activity entrained to excessive cortical beta oscillations following dopamine depletion. Zolpidem binds to GABAA receptors at the benzodiazepine site, potentiating inhibitory postsynaptic currents with selectivity for receptors expressing the α1 subunit. Coincidentally, the nuclei expressing the α1 subunit within the BG are also those that have been shown to have increased synchronous bursting activity in a dopamine-depleted state. We hypothesize that this differential expression of the α1 subunit indicates zolpidem-sensitive GABAA receptors may constitute a potential non-dopaminergic therapeutic intervention in the treatment of PD motor symptoms. The work described in this dissertation explores this possibility using behavioral neuropharmacology and analytical chemistry.