The Effects of the β-Lactam Antibiotic, Ceftriaxone, on Forepaw Stepping and l-DOPA-Induced Dyskinesia in a Rodent Model of Parkinson’s Disease
Abstract
Rationale Glutamate receptor antagonists can improve the symptoms of Parkinson's disease (PD) and reduce L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in both animal models and humans, but usually produce intolerable side effects. Recent evidence suggests that upregulation of the major glutamate transporter, GLT-1, by the β-lactam antibiotic, ceftriaxone, can increase the removal of synaptic glutamate without producing noticeable side effects, and may provide an effective alternative to receptor antagonists for several neurodegenerative diseases.Objectives We examined whether repeated i.p. injections of ceftriaxone would, like glutamate antagonists, reduce the deficits in contralateral forepaw stepping produced by unilateral injections of 6-OHDA into the medial forebrain bundle of rats and reduce LID (as measured by abnormal involuntary movements).Methods and results In Experiment 1, daily injections of 100 mg/kg ceftriaxone improved contralateral forepaw stepping by 44%, and these therapeutic effects were still apparent 29 days following the cessation of treatment. In Experiment 2, daily injections of 50 mg/kg ceftriaxone were as effective as daily injections of 10 mg/kg L-DOPA in increasing contralateral forepaw stepping by 40%. These therapeutic effects of ceftriaxone were decreased by an injection of 10 mg/kg of the selective GLT-1 antagonist, dihydrokainate (DHK), and were still evident 69 days after the cessation of ceftriaxone injections. Furthermore, ceftriaxone did not produce dyskinesia by itself and reduced the development, but not the expression, of LID.Conclusions These data suggest that ceftriaxone, by producing a long-term increase in GLT-1 function and increasing the removal of synaptic glutamate, may offer several advantages over L-DOPA as therapy for PD.
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CTX administration reverts motor impairment in PD models.
“As a consequence, dyskinesia, motor impairment and memory loss were all reverted upon CTX administration [233,234,237,238,239,240,242,243,244], although conflicting evidence still remains about its ability to improve learning outcomes [245].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [243]
CTX administration reverts memory loss in PD models.
“As a consequence, dyskinesia, motor impairment and memory loss were all reverted upon CTX administration [233,234,237,238,239,240,242,243,244], although conflicting evidence still remains about its ability to improve learning outcomes [245].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [243]
CTX administration reverts dyskinesia in PD models.
“As a consequence, dyskinesia, motor impairment and memory loss were all reverted upon CTX administration [233,234,237,238,239,240,242,243,244], although conflicting evidence still remains about its ability to improve learning outcomes [245].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [243]
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- Authors
- Kelsey, J. E., & Neville, C.
- Affiliations
- Bates College (US)
- Corresponding author
- Kelsey, John E.
- Venue
- Psychopharmacology
- Published
- 2014-01-09
- Volume
- 231
- Issue
- 12
- Pages
- 2405-2415
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2050199833
- Cited by
- 30
- References
- 37
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 2
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ceftriaxone, Parkinson's disease, levodopa-induced dyskinesia, glutamate transporter GLT-1, 6-hydroxydopamine, dihydrokainate, glutamate receptor antagonists, rodent models
- MeSH terms
- Animals, Anti-Bacterial Agents, Antiparkinson Agents, Ceftriaxone, Central Nervous System Agents, Dyskinesia, Drug-Induced, Forelimb, Kainic Acid, Levodopa, Male, Medial Forebrain Bundle, Motor Activity, Oxidopamine, Rats, Long-Evans, Parkinsonian Disorders, Excitatory Amino Acid Transporter 2
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