Poster session 4, Abstracts 1131–1166

Studies in animal models of Parkinson’s disease (PD) and preliminary clinical trials have\udshown that adenosine A2A antagonists might be useful in the treatment of the disease. In\udorder to study the effect of A2A blockade on parkinsonian tremor and on long-term\udmodifications produced by chronic L-DOPA, we have evaluated: (i) the effect of the A2A\udantagonist SCH 58261 on jaw tremor induced by tacrine; (ii) GAD 67 mRNA in basal\udganglia, by in situ hybridization in 6-hydroxydopamine (6-OHDA) lesioned rats chronically\udtreated with SCH 58261 + L-DOPA or L-DOPA alone, as model of dyskinesia. (i)\udIntact rats receiving tacrine (2.5 mg/kg) display bursts of jaw movements, which were\udcounteracted by parenteral administration of SCH 58261 (5 mg/kg). (ii) Acute administration\udof SCH 58261 + L-DOPA, potentiates the rotational behaviour induced by LDOPA\udindicating anti PD activity of A2A antagonists. Chronic administration of SCH\ud58261 (5 mg/kg) plus L-DOPA (3 mg/kg) or L-DOPA (6 mg/kg) alone, at doses producing\udthe same intensity of rotational behaviour during the first administration, showed not\udchanges and an increase in GAD67 mRNA in the GP respectively. Moreover, in the SNr, a\udsignificant decrease in GAD67 mRNA was observed after both treatments. However, while\udL-DOPA (6 mg/kg) decreased GAD67 mRNA below the intact side, SCH 58261 plus\udL-DOPA (3 mg/kg) brought the GAD67 mRNA level increased by the lesion, to the same\udlevel of the intact SNr. Antagonism of A2A receptors effectively counteracts the motor\udimpairment and tremor, which characterize PD. Moreover, long-term L-DOPA administration\udproduces changes in basal ganglia activity which appear to be responsible of\uddyskinetic effects, whereas chronic administration of A2A antagonists + L-DOPA produces\udlittle or no changes in basal ganglia suggesting that this treatment has low dyskinetic\udpotential