Fluoroquinolones (FQs) are a broad class of antibiotics typically prescribed for bacterial infections, including infections for which their use is discouraged. The FDA has proposed the existence of a permanent disability (Fluoroquinolone Associated Disability; FQAD), which is yet to be formally recognized. Previous studies suggest that FQs act as selective GABAA receptor inhibitors, preventing the binding of GABA in the central nervous system. GABA is a key regulator of the vagus nerve, involved in the control of gastrointestinal (GI) function. Indeed, GABA is released from the Nucleus of the Tractus Solitarius (NTS) to the Dorsal Motor Nucleus of the vagus (DMV) to tonically regulate vagal activity. The purpose of this review is to summarize the current knowledge on FQs in the context of the vagus nerve and examine how these drugs could lead to dysregulated signaling to the GI tract. Since there is sufficient evidence to suggest that GABA transmission is hindered by FQs, it is reasonable to postulate that the vagal circuit could be compromised at the NTS-DMV synapse after FQ use, possibly leading to the development of permanent GI disorders in FQAD.

IntroductionChildhood adversity is pervasive and linked to numerous disadvantages in adulthood, including physical health problems, mental illness, and substance use disorders. Initial sensitivity to the rewarding effects of alcohol predicts the risk of developing an alcohol use disorder, and may be linked to developmental stress. The opioid peptide β-endorphin (β-E) regulates the stress response and is also implicated in the risk for excessive alcohol consumption.MethodsWe explored the influence of β-E in an animal model of early life adversity using controlled maternal separation by evaluating changes in locomotor activity, anxiety-like behavior, and the initial rewarding effects of alcohol in a single exposure conditioned place preference paradigm in control C57BL/6J and β-E deficient β-E +/+ 0.129S2-Pomc tm1Low/J; β-E −/− mice. Maternal separation (MS) occurred for 3 h each day from post-natal days (PND) 5–18 in approximately half the subjects.ResultsMaternal interactions increased following the separation protocol equally in both genotypes. MS and control subjects were tested as adolescents (PND 26–32) or adults (PND 58–72); the effects of MS were generally more pronounced in older subjects. Adults were more active than adolescents in the open field, and MS decreased activity in adolescent mice but increased it in adults. The increase in adult activity as a result of early life stress depended on both β-E and sex. β-E also influenced the effect of maternal separation on anxiety-like behavior in the Elevated Plus Maze. MS promoted rewarding effects of alcohol in male β-E deficient mice of either age, but had no effect in other groups.DiscussionTaken together, these results suggest that the effects of MS develop over time and are β-E and sex dependent and may aid understanding of how individual differences influence the impact of adverse childhood experiences.

Background and Objectives: Fluoroquinolones (FQs) are a broad-spectrum class of antibiotics routinely prescribed for common bacterial infections despite recent recommendations to use them only for life-threatening cases. In addition to their antimicrobial properties, FQs act in the central nervous system as GABAA receptor inhibitors, which could potentially affect functionality of the vagus nerve at the forefront of gastrointestinal (GI) tract function. Alterations in neural control of digestion have been shown to be linked to Functional Gastrointestinal Disorders (FGIDs), which are usually diagnosed based on self-reported symptoms. The aim of this study was to assess the incidence of FGIDs following FQ use. Materials and Methods: Self-reports from the FDA Adverse Event Reporting System were analyzed together with ~300 survey responses from a social network derived sample to the Bowel Disease Questionnaire. Results: The results of this study suggested that six different FQs are associated with a wide range of GI symptoms not currently reported in the drugs’ labels. The responses from the survey suggested that ~70% of FQ users scored positive for FGID, with no positive correlation between drug type, duration of administration, dosage and frequency of administration. Conclusions: This study showed that GI disorders other than nausea, vomiting and diarrhea are more common than currently reported on the drug labels, and that FGIDs are possibly a common consequence of FQ use even after single use.