Adenosine A(2A) receptors are a new target for drug development in Parkinson´s disease. Some experimental and clinical data suggest that A(2A) receptor antagonists can provide symptomatic improvement by potentiating the effects of (L)-DOPA as well as a decrease in secondary effects such as (L)-DOPA-induced dyskinesia. (L)-DOPA-induced behavioral sensitization in unilateral 6-hydroxydopamine-lesioned rats is frequently used as an experimental model of (L)-DOPA-induced dyskinesia. In the present work this model was used to evaluate the effect of the A(2A) receptor agonist CGS 21680 and the AA receptor antagonist MSX-3 on (L)-DOPA-induced behavioral sensitization and 6-hydroxydopamine-induced striatal dopamine denervation. (L)-DOPA-induced behavioral sensitization was determined as an increase in (L)-DOPA-induced abnormal involuntary movements and enhancement of apomorphine-induced turning behavior. Striatal dopamine innervation was determined by measuring tyro sine-hydroxylase immunoreactivity. Chronic administration of MSX-3 was not found to be effective at counteracting (L)-DOPA-induced behavioral sensitization. On the other hand, CGS 21680 completely avoided the development of (L)-DOPA-induced behavioral sensitization. The analysis of the striatal dopamine innervation showed that (L)-DOPA-CGS 21680 co-treatment conferred neuroprotection to the toxic effects of 6-hydroxydopamine. This neuroprotective effect was dependent on A(2A) and D-2 receptor stimulation, since it was counteracted by MSX-3 and by the D-2 receptor antagonist haloperidol. These results open new therapeutic avenues in early events in Parkinson´s disease.

Neuroprotective effect of L-DOPA co-administered with the adenosine A(2A) receptor agonist CGS 21680 in an animal model of Parkinson's disease / Agnati, Luigi Francesco; Leo, Giuseppina; Vergoni, Anna Valeria; E., Martinez; J., Hockemeyer; C., Lluis; R., Franco; K., Fuxe; S., Ferre. - In: BRAIN RESEARCH BULLETIN. - ISSN 0361-9230. - STAMPA. - 64:(2004), pp. 155-164.

Neuroprotective effect of L-DOPA co-administered with the adenosine A(2A) receptor agonist CGS 21680 in an animal model of Parkinson's disease

AGNATI, Luigi Francesco;LEO, Giuseppina;VERGONI, Anna Valeria;
2004-01-01

Abstract

Adenosine A(2A) receptors are a new target for drug development in Parkinson´s disease. Some experimental and clinical data suggest that A(2A) receptor antagonists can provide symptomatic improvement by potentiating the effects of (L)-DOPA as well as a decrease in secondary effects such as (L)-DOPA-induced dyskinesia. (L)-DOPA-induced behavioral sensitization in unilateral 6-hydroxydopamine-lesioned rats is frequently used as an experimental model of (L)-DOPA-induced dyskinesia. In the present work this model was used to evaluate the effect of the A(2A) receptor agonist CGS 21680 and the AA receptor antagonist MSX-3 on (L)-DOPA-induced behavioral sensitization and 6-hydroxydopamine-induced striatal dopamine denervation. (L)-DOPA-induced behavioral sensitization was determined as an increase in (L)-DOPA-induced abnormal involuntary movements and enhancement of apomorphine-induced turning behavior. Striatal dopamine innervation was determined by measuring tyro sine-hydroxylase immunoreactivity. Chronic administration of MSX-3 was not found to be effective at counteracting (L)-DOPA-induced behavioral sensitization. On the other hand, CGS 21680 completely avoided the development of (L)-DOPA-induced behavioral sensitization. The analysis of the striatal dopamine innervation showed that (L)-DOPA-CGS 21680 co-treatment conferred neuroprotection to the toxic effects of 6-hydroxydopamine. This neuroprotective effect was dependent on A(2A) and D-2 receptor stimulation, since it was counteracted by MSX-3 and by the D-2 receptor antagonist haloperidol. These results open new therapeutic avenues in early events in Parkinson´s disease.
64
155
164
Neuroprotective effect of L-DOPA co-administered with the adenosine A(2A) receptor agonist CGS 21680 in an animal model of Parkinson's disease / Agnati, Luigi Francesco; Leo, Giuseppina; Vergoni, Anna Valeria; E., Martinez; J., Hockemeyer; C., Lluis; R., Franco; K., Fuxe; S., Ferre. - In: BRAIN RESEARCH BULLETIN. - ISSN 0361-9230. - STAMPA. - 64:(2004), pp. 155-164.
Agnati, Luigi Francesco; Leo, Giuseppina; Vergoni, Anna Valeria; E., Martinez; J., Hockemeyer; C., Lluis; R., Franco; K., Fuxe; S., Ferre
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/306944
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