Minocycline relieves depressive-like behaviors of mice subjected to ropivacaine-induced seizures.

The incidence of local anesthetic toxicity (LAST) has been increasing due to the widespread use of local anesthetic procedures in various healthcare settings. Seizures, the most common manifestation of local anesthetic toxicity, have an unclear relationship with emotional behavior. In this study, we utilized a mouse model of ropivacaine-induced seizures (RIS) to investigate the associated depressive-like behaviors in both male and female mice, and to explore the potential link between hippocampal microglial activity and these behaviors. Our findings revealed that ropivacaine-induced seizures (RIS) significantly induced depressive-like behaviors, with notable sex differences. Female mice exhibited a prolonged depressive state lasting up to 14 days post-RIS, whereas male mice no longer displayed depressive-like behaviors by that time. Consistent with the behavioral outcomes, we observed a sex-dependent difference in the duration of microglial activation following RIS, with females exhibiting more persistent microglial activation compared to males. Correlation analysis revealed that the depressive-like behaviors induced by RIS were positively correlated with increased microglial activation in the hippocampus. Furthermore, Minocycline effectively prevented depressive-like behaviors, microglial activation, and the upregulation of inflammatory cytokines in the hippocampus. Collectively, our findings implied that RIS induced depressive-like behavior in a sex-dependent manner, and microglial activation in the hippocampus seems to be a contributing factor in these behavioral changes post-RIS.