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Neurobehavioral impairments in ciprofloxacin- treated osteoarthritic adult rats
Gabriella Kékesi1, Eszter Ducza2, Hristifor Gálity3
1Department of Physiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged.
Background And Purpose:
Ciprofloxacin (CIP) is a broad-spectrum antibiotic widely used in clinical practice to treat musculoskeletal infections. Fluoroquinolone-induced neurotoxic adverse events have been reported in a few case reports, all the preclinical studies on its neuropsychiatric side effects involved only healthy animals. This study firstly investigated the behavioral effects of CIP in an osteoarthritis rat model with joint destruction and pain, which can simulate inflammation-associated musculoskeletal pain. Furthermore, effects of CIP on regional brain-derived neurotrophic factor (BDNF) expression were examined given its major contributions to the neuromodulation and plasticity underlying behavior and cognition.
Methods:
Fourteen days after induction of chronic osteoarthritis, animals were administered vehicle, 33 mg/kg or 100 mg/kg CIP for five days intraperitoneally. Motor activity, behavioral motivation, and psychomotor learning were examined in a reward-based behavioral test (Ambitus) on Day 4 and sensorimotor gating by the prepulse inhibition test on Day 5. Thereafter, the prolonged BDNF mRNA and protein expression levels were measured in the hippocampus and the prefrontal cortex.
Results:
CIP dose-dependently reduced both locomotion and reward-motivated exploratory activity, accompanied with impaired learning ability. In contrast, there were no significant differences in startle reflex and sensory gating among treatment groups; however, CIP treatment reduced motor activity of the animals in this test, too. These alterations were associated with reduced BDNF mRNA and protein expression levels in the hippocampus but not the prefrontal cortex.
Conclusion:
This study revealed the detrimental effects of CIP treatment on locomotor activity and motivation/learning ability during osteoarthritic condition, which might be due to, at least partially, deficient hippocampal BDNF expression and ensuing impairments in neural and synaptic plasticity.
Insights
Ciprofloxacin (CIP) negatively impacts motor activity and learning in osteoarthritis rats, potentially due to reduced hippocampal brain-derived neurotrophic factor (BDNF) levels.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Models
Background:
- Ciprofloxacin (CIP) is a broad-spectrum antibiotic used for musculoskeletal infections.
- Neurotoxic adverse events are reported, but preclinical studies often use healthy animals.
- This study examines CIP's effects in an osteoarthritis rat model simulating pain.
Purpose of the Study:
- Investigate behavioral effects of CIP in an osteoarthritis rat model.
- Examine CIP's impact on brain-derived neurotrophic factor (BDNF) expression in specific brain regions.
- Correlate behavioral changes with BDNF levels.
Main Methods:
- Osteoarthritis induced in rats; treated with vehicle or CIP (33, 100 mg/kg) for five days.
- Behavioral tests included motor activity, motivation (Ambitus), and sensorimotor gating (prepulse inhibition).
- BDNF mRNA and protein levels measured in hippocampus and prefrontal cortex.
Main Results:
- CIP dose-dependently reduced locomotion and motivated exploration, impairing learning.
- No significant changes in startle reflex or sensory gating, though motor activity decreased.
- Reduced hippocampal BDNF mRNA and protein levels observed; no change in prefrontal cortex.
Conclusions:
- CIP treatment detrimentally affects locomotor activity and motivation/learning in osteoarthritic rats.
- These effects may stem from deficient hippocampal BDNF expression.
- Potential impairments in neural and synaptic plasticity contribute to observed behavioral changes.
