Effects of L-Dopa on circadian rhythms of 6-OHDA striatal lesioned rats: a radiotelemetric study
Abstract
Temporal variation in the motor function of Parkinson's disease (PD) patients suggests the potential importance of a chronobiological and chronopharmacological approach in its clinical management. We previously documented the effects of striatal injection of 6-OHDA (as an animal model of PD) on the circadian rhythms of temperature (T), heart rate (HR), and locomotor activity (A). The present work assessed the possible influence of L-Dopa on these same rhythms in the 6-OHDA animal model of PD. The study began after a four-week recovery period following surgical implantation of telemetric devices to monitor the study variables and/or anaesthesia. The study was divided into an initial one-week control period (W1) for baseline measurement of T, HR, and A rhythms. Thereafter, stereotaxic 6-OHDA lesioning was done. and a second monitoring for two weeks followed (W2, W3). Rats were then randomly divided into two groups: eight control rats received, via a mini-osmotic pump implanted subcutaneously, the excipient saline; the other eight rats received L-Dopa (100 mg/kg SC/day). After a seven-day period (W4), the pumps were removed and the T, HR, and A rhythms were monitored for two weeks (W5 and W6). To control for 6-OHDA striatal dopamine-induced depletion, 12 other rats were injected by identical methods (eight rats with 6-OHDA and four controls with saline) and sacrificed at W1, W3, and W5 for dopamine striatal content determination. To verify the delivery of levodopa from the osmotic pumps, plasma levels of levodopa and its main metabolites 3-OMD, DOPAC, and HVA were determined on separate group of rats receiving the drug under the same experimental conditions (osmotic pumps delivering continuously 10 microl/h for seven days, 100 mg/kg/subcutaneously). Our results agree with previously reported rhythmic changes induced by 6-OHDA--loss of circadian rhythmicity or changes in the main parameters of the registered rhythms. When circadian rhythmicity was abolished, L-Dopa treatment improved or accelerated recovery of the circadian rhythms, the effect being more pronounced for the HR rhythm. When circadian rhythms were not abolished but perturbed, L-Dopa treatment did not improve the 6-OHDA-induced changes in the T and A mesor (24 h mean level), while a significant effect was observed for HR. It appears that constant-rate L-Dopa infusion is unable to totally balance dopamine depletion; taking into account the circadian pattern of many structures implicated in drug effect, a sinusoidal delivery of L-Dopa must be evaluated in future experiments.
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6-OHDA models exhibit disruptions in circadian rhythms of locomotion, temperature and heart rate, which are at least partially reversible by l-DOPA administration.
“The 6-OHDA models exhibit disruptions in circadian rhythms of locomotion, temperature and heart rate, which are at least partially reversible by l-DOPA administration (Boulamery et al., 2010).”
From Circadian dysregulation in Parkinson's disease (2017) · cites this paper as Boulamery et al., 2010
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- Authors
- Boulamery, A., Simon, N., Vidal, J., & Bruguerolle, B.
- Corresponding author
- Bruguerolle, Bernard
- ORCID
- Simon, Nicolas
- Venue
- Chronobiology International
- Publisher
- Informa UK Limited
- Published
- 2010-03
- Volume
- 27
- Issue
- 2
- Pages
- 251-264
- ISSN
- 0742-0528 (ISSN-L)
- 1525-6073
- OpenAlex
- W2050707194
- Cited by
- 38
- References
- 20
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 4
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chronobiology International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- L-DOPA, Parkinson's disease, 6-hydroxydopamine, striatal dopamine depletion, circadian rhythm, chronopharmacology, chronobiology, body temperature rhythm, heart rate rhythm, locomotor activity, dopamine depletion, radio telemetry, Parkinson's disease model
- MeSH terms
- Animals, Circadian Rhythm, Corpus Striatum, Dopamine, Humans, Levodopa, Motor Activity, Parkinson Disease, Sympatholytics, Telemetry, Oxidopamine, Rats, Wistar, Rats
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