Sex differences in the antidepressant-like effects of ketamine in an inflammatory mouse model of depression

A major discovery in the treatment of major depression was the finding that a single sub-anesthetic dose of ketamine induces both acute and sustained antidepressant effects in patients. Although women report major depression at twice the rate of men, the vast majority of research on ketamine’s antidepressant effects has been focused on the male sex. By inducing neuroinflammation in rodents using the pro-inflammatory agent lipopolysaccharide (LPS), a sickness syndrome is manifested with many behavioral and physiological manifestations that overlap with the clinical symptoms of major depression. The majority of studies investigating the neurobiological effects of LPS have been conducted in the male sex. The antidepressant-like effects of ketamine have only been documented in male LPS-exposed mice. Of note, female responsiveness to ketamine in this neuroinflammatory model of depression remains elusive. In this study, we are investigating the sex differentiated antidepressant effects of both acute and chronic treatment of ketamine on the LPS-induced neuroinflammatory model of depression. Preliminary data from acute ketamine treatment points to a differentiation in behavior in male and female mice. In addition to this preliminary data, we are currently conducting the chronic ketamine administration phase of the study. Data collected by our lab is promising in the search for novel mechanisms for female ketamine response under the neuroinflammatory model of depression