In vivo and in vitro evidence of dopaminergic system down regulation induced by chronic L-DOPA

• Published in: Life sciences (1973) Vol. 34; no. 22; p. 2107
• Main Authors: Ponzio, F, Cimino, M, Achilli, G, Lipartiti, M, Perego, C, Vantini, G, Algeri, S
• Format: Journal Article
• Language: English
• Published: Netherlands 28-05-1984
• Subjects: Animals; Apomorphine - pharmacology; Benserazide - pharmacology; Binding Sites; Cell Membrane - metabolism; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - analogs & derivatives; Dopamine - metabolism; Hydrazines - pharmacology; Levodopa - pharmacology; Male; Rats; Rats, Inbred Strains; Receptors, Dopamine - metabolism; Spiperone - metabolism; Tetrahydronaphthalenes - metabolism; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(84)90309-6

The biochemical modifications which occur in the dopaminergic system after chronic administration of L-DOPA are investigated. Levels of DA and of its metabolite 3-methoxytyramine (3-MT), an expression of the amount of DA released, were raised to the same extent in controls given a single dose of 1-DOPA and in chronically treated rats given 100 mg/kg of 1-DOPA plus 25 mg/kg of benserazide twice a day for 24 days. However, the reduction in neuronal function expressed by the decrease in 3-MT which follows treatment with DA agonists such as piribedil and apomorphine was less pronounced in the chronically L-DOPA treated rats. This suggests that such treatment causes a down regulation of DA receptors. These in vivo results were confirmed by in vitro analysis of DA receptor activity after chronic L-DOPA. Under these conditions there was a significant reduction in the number of [3H]-spiperone and [3H]-ADTN binding sites with no changes in their affinity. The in vivo and in vitro findings both suggest the involvement of a subsensitive compensatory mechanism or down regulation of dopaminergic neurons after chronic treatment with L-DOPA.