Chronic administration of L-DOPA to MPTP-treated common marmosets induces marked dyskinesia whilerepeated administration of equivalent antiparkisonian doses of ropinirole and bromocriptine produces only mild involuntarymovements. The occurrence of dyskinesia has been associated with an altered balance between the direct andindirect striatal output pathways. Using in situ hybridisation histochemistry, we now compare the e¡ects of these drugtreatments on striatal preproenkephalin-A (PPE-A) and adenosine A2a receptor mRNA expression as markers of theindirect pathway and striatal preprotachykinin (PPT) mRNA and preproenkephalin-B (PPE-B, prodynorphin) mRNAexpression as markers of the direct pathway.The equivalent marked losses of speci¢c [3H]mazindol binding in the striatum of all drug treatment groups con¢rmedthe identical nature of the nigral cell loss produced by MPTP treatment. MPTP-induced destruction of the nigro-striatalpathway markedly increased the level of PPE-A mRNA in the caudate nucleus and putamen and decreased the levels ofPPT and PPE-B mRNA relative to normal animals. Repeated treatment with L-DOPA for 30 days produced markeddyskinesia but had no e¡ect on the MPTP-induced increase in PPE-A mRNA in the caudate nucleus and putamen. Incontrast, L-DOPA treatment normalised the MPTP-induced decrease in the level of PPT and PPE-B mRNA. Repeatedtreatment with ropinirole produced little or no dyskinesia but markedly reversed the MPTP-induced elevation in PPE-AmRNA in the caudate nucleus and putamen. However, it had no e¡ect on the decrease in PPT or PPE-B mRNA.Similarly, bromocriptine treatment which induced only mild dyskinesia attenuated the MPTP-induced elevation in PPE-AmRNA in the caudate nucleus and putamen with no e¡ect on reduced striatal PPT or PPE-B mRNA. Neither MPTPtreatment nor treatment with L-DOPA, bromocriptine or ropinirole had any e¡ect on adenosine A2a receptor mRNA inthe striatum.These patterns of alteration in striatal PPE-A and PPT and PPE-B mRNA produced by L-DOPA, bromocriptine andropinirole show di¡erential involvement of markers of the direct and indirect striatal output pathways related to improvementof locomotor activity and mirror the relative abilities of the drugs to induce dyskinesia.
|Numero di pagine||12|
|Stato di pubblicazione||Published - 2002|
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