Title:  Dopamine and adenosine receptor interaction as the basis for the treatment of Parkinson's disease
Internal authors: 
Issue Date:  2004
Abstract:  Studies in animal models of Parkinson’s disease (PD) and preliminary clinical trials have shown that adenosine A2A antagonists might be useful in the treatment of the disease. In order to study the effect of A2A blockade on parkinsonian tremor and on long-term modifications produced by chronic L-DOPA, we have evaluated: (i) the effect of the A2A antagonist SCH 58261 on jaw tremor induced by tacrine; (ii) GAD 67 mRNA in basal ganglia, by in situ hybridization in 6-hydroxydopamine (6-OHDA) lesioned rats chronically treated with SCH 58261 + L-DOPA or L-DOPA alone, as model of dyskinesia. (i) Intact rats receiving tacrine (2.5 mg/kg) display bursts of jaw movements, which were counteracted by parenteral administration of SCH 58261 (5 mg/kg). (ii) Acute administration of SCH 58261 + L-DOPA, potentiates the rotational behaviour induced by LDOPA indicating anti PD activity of A2A antagonists. Chronic administration of SCH 58261 (5 mg/kg) plus L-DOPA (3 mg/kg) or L-DOPA (6 mg/kg) alone, at doses producing the same intensity of rotational behaviour during the first administration, showed not changes and an increase in GAD67 mRNA in the GP respectively. Moreover, in the SNr, a significant decrease in GAD67 mRNA was observed after both treatments. However, while L-DOPA (6 mg/kg) decreased GAD67 mRNA below the intact side, SCH 58261 plus L-DOPA (3 mg/kg) brought the GAD67 mRNA level increased by the lesion, to the same level of the intact SNr. Antagonism of A2A receptors effectively counteracts the motor impairment and tremor, which characterize PD. Moreover, long-term L-DOPA administration produces changes in basal ganglia activity which appear to be responsible of dyskinetic effects, whereas chronic administration of A2A antagonists + L-DOPA produces little or no changes in basal ganglia suggesting that this treatment has low dyskinetic potential.
URI:  http://hdl.handle.net/11584/97646
Type: 1.5 Abstract in rivista

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