The effects of chronic continuous versus intermittent levodopa treatments on striatal and extrastriatal D1 and D2 dopamine receptors and dopamine uptake sites in the 6-hydroxydopamine lesioned rat — an autoradiographic study
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Abstract
The effects of chronic 'continuous' infusion and 'intermittent' modes of levodopa/carbidopa
administration on apomorphine induced circling behaviour, DA uptake sites (labelled
with [3H]mazindol) and D1 and D2 DA receptor binding (labelled with [3H]SCH 23390
and [3H]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' regime, the lower dose of apomorphine induced
a period of intense circling with delayed onset and rapid offset, than in rats given
either 'continuous' infusion of levodopa or saline. The 6-OHDA lesion itself induced
gross depletion of [3H]mazindol binding in all striatal subregions, NAc and OT, but
not frontal cortex. [3H]Sulpiride binding in the ventrolateral striatal quadrant was
increased on the denervated side and this correlated with the peak contralateral turns
in response to 0.5 mg/kg apomorphine challenge. This asymmetry in striatal [3H]sulpiride
binding was reduced in both groups of rats receiving levodopa. [3H]sulpiride binding
in the NAc and OT and [3H]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 'intermittent' injections of levodopa reduced [3H]mazindol binding
in the striatal subregions and the frontal cortex on both the denervated and intact
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 receptors. In the same group of animals the narrowing of the duration
of response to the lower dose of apomorphine may mimic the fluctuations in response
to levodopa, seen clinically in long-term levodopa treated parkinsonian patients.