Effects of repeated methyl levodopa administration on apomorphine sensitivity of rotational behavior and striatal Fos expression of rats with unilateral 6-OHDA lesions

This study was designed to elucidate the mechanism to develop levodopa-indu ced dyskinesia in patients with Parkinson's disease. For this purpose, we a dministered methyl levodopa repeatedly to a, rat model of Parkinson's disea se with unilateral 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrost riatal dopamine pathway. After a washout period, we measured apomorphine se nsitivity of contralateral rotation and made parallel determination of Fos expression in the caudate-putamen and globus pallidus of the same animal. O nce daily, i.p. injection of methyl levodopa plus benserazide for 10 days; increased the number of rotations over time. A challenge dose of apomorphin e showed enhanced rotational response in rats pretreated with methyl levodo pa. Repeated administration of methyl levodopa resulted in diminished apomo rphine sensitivity of Fos expression in the dopamine depleted caudate-putam en and in enhanced sensitivity in the globus pallidus of the same side. Pre sent results may add evidence to the idea that repeated administration of l evodopa develops dopaminergic sensitization mediated by augmented activatio n of pallidal neurons involved in D2-responsive pallidal output pathway. (C ) 2000 Elsevier Science Ireland Ltd and Japan Neuroscience Society.