Brain Advance Access published online on May 20, 2004
Brain, doi:10.1093/brain/awh190
© 2004 by Guarantors of Brain
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1 Dipartimento di Neuroscienze, Clinica Neurologica, Università di Roma ‘Tor Vergata’, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy
* To whom correspondence should be addressed. E-mail: calabre{at}uniroma2.it.
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. Key Words:
basal ganglia; dopamine; excitatory synaptic transmission; Parkinson’s disease
Revised March 12, 2004
Accepted March 14, 2004
Article
Therapeutic doses of L-dopa reverse hypersensitivity of corticostriatal D2-dopamine receptors and glutamatergic overactivity in experimental parkinsonism
2 Dipartimento di Neuroscienze, Clinica Neurologica, Università di Roma ‘Tor Vergata’, Rome, Italy IRCCS Fondazione Santa Lucia, Rome, Italy
3 Dipartimento di Neuroscienze, Clinica Neurologica, Università di Roma ‘Tor Vergata’, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy; Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma ‘Tor Vergata’, Via Montpellier 1, Rome 00133, Italy
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