Interval-dependent neurotoxicity after multiple ketamine injections in late postnatal mice

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

“…for 5 consecutive days (PND16–20). The anesthetic dose of ketamine was based on our previous study, where we found that higher doses occasionally caused prolonged anesthesia or mortality (>40 mg kg −1 , i.p) 26 . Unlike other anesthetic agents, clinical studies have reported acute tolerance after repeated ketamine anesthesia in children 31 , 32 .…”

“…Although sex is recognized as an important biological factor 44 , we did not initially perform experiments in female mice. This was based on our recent study, where we reported non-sex-dependent changes after repeated ketamine anesthesia (two-way ANOVA) 26 . However, another recent study reported conflicting results by showing that repeated ketamine treatment in young mice enhanced place preference for cocaine only in male mice 41 .…”

“…Mice were randomly divided into two groups at PND16 (Control and Anesthesia group). Mice in the Anesthesia group received daily intraperitoneal injections of ketamine (35 mg kg −1 ) for 5 consecutive days 26 . Although the majority of preclinical studies exposed young animals to 3 episodes of anesthesia, ketamine is often used outside the operating room for more frequently repeated short-term procedures or radiographic examinations 31 , 32 .…”

“…Sample sizes were based on the previous studies 12 , 26 , 41 . For electrophysiological data, the average of each animal (at least 2 cells per animal) was used.…”

“…As a result of these attributes, ketamine has come to be used as a recreational drug at sub-anesthetic doses, leading to drug abuse 25 . Since ketamine exposures during neurodevelopment induce E/I imbalance 26 , 27 , and ketamine itself has addictive properties, we hypothesized that repeated ketamine anesthesia during neurodevelopment might affect addiction behavior later in life.…”