THE EFFECTS OF CHRONIC CONTINUOUS VERSUS INTERMITTENT LEVODOPA TREATMENTS ON STRIATAL AND EXTRASTRIATAL D(1) AND D(2) DOPAMINE-RECEPTORS AND DOPAMINE UPTAKE SITES IN THE 6-HYDROXYDOPAMINE LESIONED RAT - AN AUTORADIOGRAPHIC STUDY

The effects of chronic 'continuous' infusion and 'intermittent' modes of levodopa/carbidopa administration on apomorphine induced circling b ehaviour, DA uptake sites (labelled with [H-3]mazindol) and D1 and D2 DA receptor binding (labelled with [H-3]SCH 23390 and [H-3]sulpiride, respectively) were investigated in rats with unilateral 6-OHDA lesions of the medial forebrain bundle. The circling behaviour in response to apomorphine was greatly enhanced following chronic 'intermittent' but not 'continuous' levodopa treatments. Following the 'intermittent' re gime, the lower dose of apomorphine induced a period of intense circli ng with delayed onset and rapid offset, than in rats given either 'con tinuous' infusion of levodopa or saline. The 6-OHDA lesion itself indu ced gross depletion of [H-3]mazindol binding in all striatal subregion s, NAc and OT, but not frontal cortex. [H-3]Sulpiride binding in the v entrolateral striatal quadrant was increased on the denervated side an d this correlated with the peak contralateral turns in response to 0.5 mg/kg apomorphine challenge. This asymmetry in striatal [H-3]sulpirid e binding was reduced in both groups of rats receiving levodopa. [H-3] sulpiride binding in the NAc and OT and [H-3]SCH 23390 binding in the striatum, NAc, OT and SNr were unaffected by DA denervation or either regime of levodopa treatments. 'Continuous' infusion and not 'intermit tent' injections of levodopa reduced [H-3]mazindol binding in the stri atal subregions and the frontal cortex on both the denervated and inta ct sides. The potentiation of the behavioural response to apomorphine by chronic 'intermittent' levodopa treatment does not correspond with the levodopa induced alterations in striatal or extrastriatal DA recep tors. In the same group of animals the narrowing of the duration of re sponse to the lower dose of apomorphine may mimic the fluctuations in response to levodopa, seen clinically in long-term levodopa treated pa rkinsonian patients.