MODULATORY EFFECTS OF L-DOPA ON D2 DOPAMINE-RECEPTORS IN RAT STRIATUM, MEASURED USING IN-VIVO MICRODIALYSIS AND PET

Putative modulatory effects of L-3,4-dihydroxyphenylalanine (L-DOPA) o n D2 dopamine receptor function in the striatum of anaesthetised rats were investigated using both in vivo microdialysis and positron emissi on tomography (PET) with carbon-ii labelled raclopride as a selective D2 receptor ligand. A single dose of L-DOPA (20 or 100mg/kg i.p.) resu lted in an increase in [C-11]raclopride binding potential which was al so observed in the presence of the central aromatic decarboxylase inhi bitor NSD 1015, confirming that the effect was independent of dopamine . This L-DOPA evoked D2 receptor sensitisation was abolished by a prio r, long-term administration of L-DOPA, in drinking water (5 weeks, 170 mg/kg/day). In the course of acute L-DOPA treatment (20 mg/kg): extrac ellular GABA levels were reduced by similar to 20% in the globus palli dus. It is likely that L-DOPA sensitising effect on striatal D2 recept ors, as confirmed by PET, may implicate striato-pallidal neurones, hen ce a reduced GABA-ergic output in the projection area. Since the L-DOP A evoked striatal D2 receptor supersensitivity habituates during long- term treatment, the effects reported here may contribute to the fluctu ations observed during chronic L-DOPA therapy in Parkinson's disease.