Ciprofloxacin May Cause an Anxiety‐like Phenotype in a Rodent Model of Fluoroquinolone Associated Disability

Abstract

Fluoroquinolones (FQ) are one of the most commonly prescribed antibiotics used to treat several infections including urinary tract infections, bacterial bronchitis, and bacterial gastroenteritis. However, the FDA has restricted their use to life‐threatening infections only, or for infections for which other antibiotics do not show therapeutic efficacy. The most frequent side‐effects reported include common gastrointestinal reactions (nausea, vomiting) and severe side effects, including Central Nervous System adverse reactions such as dizziness, insomnia, and severe mood disorders. For this reason, the existence of Fluoroquinolones‐Associated Disability has been proposed as the constellation of disabling side effects that may arise following administration of these antibiotics. Other preliminary data from our laboratory shows that administration of 20 mg/kg of ciprofloxacin (CPX), one of the most commonly prescribed FQs, permanently accelerates gastrointestinal transit. The goal of this study is to test whether the same dosage of CPX affects anxiety‐ and depression‐like behaviors in rats, and whether or not these behavioral changes are correlated to the observed gastrointestinal dysfunction. 3 males and 3 female rats received 20mg/kg of CPX through oral gavage once a day for 14 consecutive days. The Elevated plus‐maze test (EPM) and Sucrose Preference Test (SPT) were administered before the beginning of the treatment with CPX (baseline) and once weekly for a total of 4 weeks. At this dose, CPX did not affect the rats' preference for 1% sucrose water vs regular water in the SPT test. However, while we did not observe any differences in the time spent in the open or closed arm, nor in the number of entries in either arms, the EPM test showed that there was a significant difference in the time spent in the neutral zone for male CPX treated rats at 7, 21, and 28 testing days compared to baseline. This data shows that 20 mg/kg of CPX do not induce anhedonia, a measure of depression‐like behavior, but can induce an anxious phenotype in male rats only, which does not appear to be associated with the observed acceleration of gastrointestinal transit. Future experiments will determine whether this behavior is associated with an increase in anxiety, as observed in numerous clinical cases, or if it is caused by either a decrease in motor performance or cognitive abilities following CPX administration.