Tags

Type your tag names separated by a space and hit enter

l-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation.
Neurobiol Dis. 2008 Feb; 29(2):327-35.ND

Abstract

The emergence of levodopa (l-DOPA)-induced dyskinesia and motor fluctuations represents a major clinical problem in Parkinson's disease (PD). While it has been suggested that the daily dose of l-DOPA can play a critical role, the mechanisms linking l-DOPA dosage to the occurrence of motor complications have not yet been explored. Using an experimental model of PD we have recently demonstrated that long-term l-DOPA treatment leading to the induction of abnormal involuntary movements (AIMs) alters corticostriatal bidirectional synaptic plasticity. Dyskinetic animals, in fact, lack the ability to reverse previously induced long-term potentiation (LTP). This lack of depotentiation has been associated to a defect in erasing unessential motor information. Here chronic l-DOPA treatment was administered at two different doses to hemiparkinsonian rats, and electrophysiological recordings were subsequently performed from striatal spiny neurons. Both low and high doses of l-DOPA restored normal LTP, which was disrupted following dopamine (DA) denervation. By the end of the chronic treatment, however, while the low l-DOPA dose induced AIMs only in half of the rats, the high dose caused motor complications in all the treated animals. Interestingly, the dose-related expression of motor complications was associated with a lack of synaptic depotentiation. Our study provides further experimental evidence to support a direct correlation between the daily dosage of l-DOPA and the induction of motor complications and establishes a critical pathophysiological link between the lack of synaptic depotentiation and the expression of AIMs.

Authors+Show Affiliations

Laboratorio di Neurofisiologia, Fondazione Santa Lucia, IRCCS c/o CERC, Rome, Italy. b.picconi@hsantalucia.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17997101

Citation

Picconi, Barbara, et al. "L-DOPA Dosage Is Critically Involved in Dyskinesia Via Loss of Synaptic Depotentiation." Neurobiology of Disease, vol. 29, no. 2, 2008, pp. 327-35.
Picconi B, Paillé V, Ghiglieri V, et al. L-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation. Neurobiol Dis. 2008;29(2):327-35.
Picconi, B., Paillé, V., Ghiglieri, V., Bagetta, V., Barone, I., Lindgren, H. S., Bernardi, G., Angela Cenci, M., & Calabresi, P. (2008). L-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation. Neurobiology of Disease, 29(2), 327-35.
Picconi B, et al. L-DOPA Dosage Is Critically Involved in Dyskinesia Via Loss of Synaptic Depotentiation. Neurobiol Dis. 2008;29(2):327-35. PubMed PMID: 17997101.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - l-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation. AU - Picconi,Barbara, AU - Paillé,Vincent, AU - Ghiglieri,Veronica, AU - Bagetta,Vincenza, AU - Barone,Ilaria, AU - Lindgren,Hanna S, AU - Bernardi,Giorgio, AU - Angela Cenci,M, AU - Calabresi,Paolo, Y1 - 2007/10/11/ PY - 2007/08/01/received PY - 2007/09/27/revised PY - 2007/10/01/accepted PY - 2007/11/13/pubmed PY - 2008/4/5/medline PY - 2007/11/13/entrez SP - 327 EP - 35 JF - Neurobiology of disease JO - Neurobiol Dis VL - 29 IS - 2 N2 - The emergence of levodopa (l-DOPA)-induced dyskinesia and motor fluctuations represents a major clinical problem in Parkinson's disease (PD). While it has been suggested that the daily dose of l-DOPA can play a critical role, the mechanisms linking l-DOPA dosage to the occurrence of motor complications have not yet been explored. Using an experimental model of PD we have recently demonstrated that long-term l-DOPA treatment leading to the induction of abnormal involuntary movements (AIMs) alters corticostriatal bidirectional synaptic plasticity. Dyskinetic animals, in fact, lack the ability to reverse previously induced long-term potentiation (LTP). This lack of depotentiation has been associated to a defect in erasing unessential motor information. Here chronic l-DOPA treatment was administered at two different doses to hemiparkinsonian rats, and electrophysiological recordings were subsequently performed from striatal spiny neurons. Both low and high doses of l-DOPA restored normal LTP, which was disrupted following dopamine (DA) denervation. By the end of the chronic treatment, however, while the low l-DOPA dose induced AIMs only in half of the rats, the high dose caused motor complications in all the treated animals. Interestingly, the dose-related expression of motor complications was associated with a lack of synaptic depotentiation. Our study provides further experimental evidence to support a direct correlation between the daily dosage of l-DOPA and the induction of motor complications and establishes a critical pathophysiological link between the lack of synaptic depotentiation and the expression of AIMs. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/17997101/l_DOPA_dosage_is_critically_involved_in_dyskinesia_via_loss_of_synaptic_depotentiation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(07)00222-7 DB - PRIME DP - Unbound Medicine ER -