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Continuous and intermittent levodopa differentially affect basal ganglia function
Author(s) -
Juncos Jorge L.,
Engber Thomas M.,
Raisman Rita,
Susel Zvi,
Thibaur Florence,
Ploska Alain,
Agid Yves,
Chase Thomas N.
Publication year - 1989
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410250509
Subject(s) - basal ganglia , levodopa , affect (linguistics) , neuroscience , parkinson's disease , psychology , biology , medicine , disease , central nervous system , communication
The effects of continuous and intermittent levodopa treatment on behavioral and biochemical indexes of basal ganglia function were compared in rats with unilateral 6‐hydroxydopamine lesions of the nigrostriatal dopamine pathway. Animals treated for 30 days with intermittent levodopa exhibited behavioral sensitization manifested by an enhanced rotational response to apomorphine; the rotational response of rats treated with an equivalent dose of levodopa by continuous infusion did not differ from that of saline‐treated controls. Dopamine receptor up‐regulation in the denervated striatum relative to the intact striatum was statistically significant for D 1 but not D 2 receptors: This asymmetry in dopamine receptor levels was diminished following intermittent levodopa treatment. Glutamic acid decarboxylase activity, modestly elevated in all groups in the denervated striatum relative to the intact striatum, increased substantially over control values bilaterally as a result of intermittent, but not continuous, levodopa treatment. These findings suggest a relation between the schedule of chronic levodopa administration and the development of behavioral sensitization, possibly as a consequence of alterations in neuronal systems located downstream from striatal dopamine receptors. The behavioral sensitization induced by chronic, intermittent dopaminomimetic treatment may serve as a model for motor fluctuations in Parkinson's disease.