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The effects of L-DOPA on gait abnormalities in a unilateral 6-OHDA rat model of Parkinson's disease.
- Source :
-
Physiology & behavior [Physiol Behav] 2024 Jul 01; Vol. 281, pp. 114563. Date of Electronic Publication: 2024 May 08. - Publication Year :
- 2024
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Abstract
- Parkinson's Disease (PD) is a neurodegenerative movement disorder characterized by dopamine (DA) cell loss in the substantia nigra pars compacta (SNc). As PD progresses, patients display disruptions in gait such as changes in posture, bradykinesia, and shortened stride. DA replacement via L-DOPA alleviates many PD symptoms, though its effects on gait are not well demonstrated. This study aimed to assess the relationship between DA lesion, gait, and deficit-induced reversal with L-DOPA. To do so, Sprague-Dawley rats (N = 25, 14 males, 11 females) received unilateral medial forebrain bundle (MFB) DA lesions with 6-hydroxydopamine (6-OHDA). An automated gait analysis system assessed spatiotemporal gait parameters pre- and post-lesion, and after various doses of L-DOPA (0, 3, or 6 mg/kg; s.c.). The forepaw adjusting steps (FAS) test was implemented to evaluate lesion efficacy while the abnormal involuntary movements (AIMs) scale monitored the emergence of L-DOPA-induced dyskinesia (LID). High performance liquid chromatography (HPLC) assessed changes in brain monoamines on account of lesion and treatment. Results revealed lesion-induced impairments in gait, inclusive of max-contact area and step-sequence alterations that were not reversible with L-DOPA. However, the emergence of AIMs were observed at higher doses. Post-mortem, 6-OHDA lesions induced a loss of striatal DA and norepinephrine (NE), while prefrontal cortex (PFC) displayed noticeable reduction in NE but not DA. Our findings indicate that hemiparkinsonian rats display measurable gait disturbances similar to PD patients that are not rescued by DA replacement. Furthermore, non-DA mechanisms such as attention-related NE in PFC may contribute to altered gait and may constitute a novel target for its treatment.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Male
Female
Rats
Antiparkinson Agents pharmacology
Disease Models, Animal
Medial Forebrain Bundle drug effects
Parkinsonian Disorders chemically induced
Parkinsonian Disorders drug therapy
Parkinsonian Disorders physiopathology
Parkinsonian Disorders pathology
Dopamine metabolism
Dose-Response Relationship, Drug
Functional Laterality drug effects
Parkinson Disease drug therapy
Parkinson Disease pathology
Parkinson Disease physiopathology
Gait drug effects
Dyskinesia, Drug-Induced
Levodopa pharmacology
Levodopa adverse effects
Oxidopamine
Rats, Sprague-Dawley
Gait Disorders, Neurologic chemically induced
Gait Disorders, Neurologic drug therapy
Gait Disorders, Neurologic etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-507X
- Volume :
- 281
- Database :
- MEDLINE
- Journal :
- Physiology & behavior
- Publication Type :
- Academic Journal
- Accession number :
- 38723388
- Full Text :
- https://doi.org/10.1016/j.physbeh.2024.114563