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Brain. 2004 Jul;127(Pt 7):1661-9. Epub 2004 May 20.

Therapeutic doses of L-dopa reverse hypersensitivity of corticostriatal D2-dopamine receptors and glutamatergic overactivity in experimental parkinsonism.

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1
Dipartimento di Neuroscienze, Clinica Neurologica, Universita di Roma 'Tor Vergata', Rome, Italy.

Abstract

Levodopa (l-dopa) therapy is still considered the gold-standard in the treatment of Parkinson's disease. However, the synaptic and cellular mechanisms involved in the amelioration of motor symptoms during this treatment are still unclear. To address this issue, we analysed the physiological and pharmacological properties of striatal glutamatergic and GABAergic synaptic transmission in an experimental model of Parkinson's disease. Single-cell recordings were performed in sham-operated rats, in 6-hydroxydopamine-lesioned animals and in rats receiving chronic l-dopa treatment following dopamine (DA) denervation. We utilized a dose of l-dopa (10 mg/kg, twice daily for 21 days) able to reverse motor deficits in about half of parkinsonian animals. In the striatum of parkinsonian animals showing therapeutic benefits following l-dopa treatment, we observed a reversal of glutamatergic overactivity and of the hypersensitivity of presynaptic D2 DA receptors controlling glutamate release from corticostriatal terminals. Conversely, no change was detected in the sensitivity of presynaptic D2 DA receptors modulating striatal GABA transmission in both parkinsonian and l-dopa-treated rats. We suggest that the reversal of striatal glutamatergic overactivity and the normalization of hypersensitive D2 DA receptors modulating excitatory transmission might underlie some of the therapeutic actions of l-dopa in Parkinson's disease.

PMID:
15155524
DOI:
10.1093/brain/awh190
[Indexed for MEDLINE]
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