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Bilateral subthalamic nucleus lesion reverses L-dopa-induced motor fluctuations and facilitates dyskinetic movements in hemiparkinsonian rats.
Synapse. 2004 Feb; 51(2):140-50.S

Abstract

Glutamatergic overactivity might be involved in L-dopa-induced motor complications since glutamate antagonists reverse and prevent L-dopa-induced shortening in motor response duration in 6-hydroxydopamine-lesioned (6-OHDA) rats and improve L-dopa-induced dyskinesias in parkinsonian monkeys and in patients with Parkinson's disease (PD). An increase in the subthalamic nucleus (STN) glutamatergic activity is believed to contribute to the pathophysiology of PD. However, the role of STN activity in L-dopa-induced motor complications is not so clear. In this study, the effect of STN lesions on L-dopa-induced motor response complications was investigated in rats with a nigrostriatal pathway lesion induced by 6-OHDA. Animals were injected with 6-OHDA in the medial forebrain bundle and treated with L-dopa or saline for 22 days. On day 16, animals were randomly distributed in groups that underwent surgery in the STN ipsilateral or contralateral to 6-OHDA lesion, or bilateral. Rotational behavior was measured on days 1, 15, and 22. Attenuation of STN activity by contralateral and bilateral, but not ipsilateral, STN lesion reversed the shortening in motor response duration induced by L-dopa. L-dopa administration, but not saline, induced prominent dyskinesias in 6-OHDA-lesioned rats with additional bilateral STN lesions. The results indicate that bilateral lesions of STN potentiate the duration of L-dopa-induced motor response and facilitate chronic L-dopa-induced abnormal involuntary movements in 6-OHDA-lesioned rats. The characteristics of the abnormal involuntary movements observed in these animals are similar to L-dopa-induced dyskinesias in parkinsonian patients and might be useful as an experimental model for the study of L-dopa-induced dyskinesia.

Authors+Show Affiliations

Laboratori de Neurologia Experimental, Fundació Clínic-Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain. cmarin@medicina.ub.esNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

14618681

Citation

Marin, Concepció, et al. "Bilateral Subthalamic Nucleus Lesion Reverses L-dopa-induced Motor Fluctuations and Facilitates Dyskinetic Movements in Hemiparkinsonian Rats." Synapse (New York, N.Y.), vol. 51, no. 2, 2004, pp. 140-50.
Marin C, Jiménez A, Tolosa E, et al. Bilateral subthalamic nucleus lesion reverses L-dopa-induced motor fluctuations and facilitates dyskinetic movements in hemiparkinsonian rats. Synapse. 2004;51(2):140-50.
Marin, C., Jiménez, A., Tolosa, E., Bonastre, M., & Bové, J. (2004). Bilateral subthalamic nucleus lesion reverses L-dopa-induced motor fluctuations and facilitates dyskinetic movements in hemiparkinsonian rats. Synapse (New York, N.Y.), 51(2), 140-50.
Marin C, et al. Bilateral Subthalamic Nucleus Lesion Reverses L-dopa-induced Motor Fluctuations and Facilitates Dyskinetic Movements in Hemiparkinsonian Rats. Synapse. 2004;51(2):140-50. PubMed PMID: 14618681.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bilateral subthalamic nucleus lesion reverses L-dopa-induced motor fluctuations and facilitates dyskinetic movements in hemiparkinsonian rats. AU - Marin,Concepció, AU - Jiménez,Anna, AU - Tolosa,Eduardo, AU - Bonastre,Mercè, AU - Bové,Jordi, PY - 2003/11/18/pubmed PY - 2004/2/11/medline PY - 2003/11/18/entrez SP - 140 EP - 50 JF - Synapse (New York, N.Y.) JO - Synapse VL - 51 IS - 2 N2 - Glutamatergic overactivity might be involved in L-dopa-induced motor complications since glutamate antagonists reverse and prevent L-dopa-induced shortening in motor response duration in 6-hydroxydopamine-lesioned (6-OHDA) rats and improve L-dopa-induced dyskinesias in parkinsonian monkeys and in patients with Parkinson's disease (PD). An increase in the subthalamic nucleus (STN) glutamatergic activity is believed to contribute to the pathophysiology of PD. However, the role of STN activity in L-dopa-induced motor complications is not so clear. In this study, the effect of STN lesions on L-dopa-induced motor response complications was investigated in rats with a nigrostriatal pathway lesion induced by 6-OHDA. Animals were injected with 6-OHDA in the medial forebrain bundle and treated with L-dopa or saline for 22 days. On day 16, animals were randomly distributed in groups that underwent surgery in the STN ipsilateral or contralateral to 6-OHDA lesion, or bilateral. Rotational behavior was measured on days 1, 15, and 22. Attenuation of STN activity by contralateral and bilateral, but not ipsilateral, STN lesion reversed the shortening in motor response duration induced by L-dopa. L-dopa administration, but not saline, induced prominent dyskinesias in 6-OHDA-lesioned rats with additional bilateral STN lesions. The results indicate that bilateral lesions of STN potentiate the duration of L-dopa-induced motor response and facilitate chronic L-dopa-induced abnormal involuntary movements in 6-OHDA-lesioned rats. The characteristics of the abnormal involuntary movements observed in these animals are similar to L-dopa-induced dyskinesias in parkinsonian patients and might be useful as an experimental model for the study of L-dopa-induced dyskinesia. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/14618681/Bilateral_subthalamic_nucleus_lesion_reverses_L_dopa_induced_motor_fluctuations_and_facilitates_dyskinetic_movements_in_hemiparkinsonian_rats_ L2 - https://doi.org/10.1002/syn.10291 DB - PRIME DP - Unbound Medicine ER -