A Method for Measuring Dissociative Effects of Sub-Anesthetic Doses of Ketamine in Juvenile Female Rats

Treatment-resistant juvenile depression is a globally prevalent issue, with a need for better pharmacotherapy. Typically, Selective Serotonin Reuptake Inhibitors are front line, but recently there is interest in examining using ketamine or esketamine adjunct in adolescents. In this study, a novel method is used to explore the adverse effects of sub-anesthetic doses of ketamine in a female pre-pubescent rat model, to assess its potential clinical implications. We assessed the severity and duration of dissociative behavior at three sub-anesthetic doses of ketamine (40, 50, and 60 mg•kg^-1). Dissociative behaviors cause a subject to feel apart from their reality and ketamine is often abused for such effects. Dissociative behaviors, such as circling and ataxia, were observed following ketamine administration, with higher doses leading to increased severity and duration of symptoms up to 120 min post-injection. Our findings revealed that increasing doses of ketamine intensified both the severity and duration of dissociative behaviors. In conclusion, these results suggest a correlation underlying ketamine's rapid-acting antidepressant effect, particularly with higher sub-anesthetic doses associated with more pronounced dissociative behaviors and a rapid-acting antidepressant effect. Further investigation into ketamine's impact on longer-term dissociative effects is warranted to deepen our understanding of its therapeutic risks of ketamine treatment of adolescent depression.