Retigabine promotes ketamine's antidepressant effect in the forced swim test in male and female C57BL/6J mice.

Adding retigabine, a KCNQ channel opener, to a low dose of ketamine that alone had no antidepressant effect produced a strong antidepressant effect in both male and female C57BL/6J mice in the forced swim test. Retigabine also prolonged the duration of ketamine's antidepressant effect. The findings suggest that adjunctive retigabine could enhance ketamine's antidepressant properties, potentially allowing lower ketamine doses and reducing its risk of dependence.

Study at a glance

Abstract

Ketamine has been increasingly used as a rapid-onset antidepressant in specific clinical settings. However, as a psychedelic reagent, the potential of physical and psychological dependence limits its clinical use. Here, we added retigabine, a KCNQ channel opener, as an adjunctive treatment to observe its effect on ketamine's antidepressant property in a forced swim test in both male and female C57BL/6 J mice. Behavioral data demonstrated that intraperitoneal injection of ketamine exhibited a dose-dependent effect on animals' immobility performance in the forced swim test. Adding retigabine was sufficient to induce a remarkable antidepressant effect in mice treated with a relatively lower dose of ketamine which failed to be antidepressant when administrated separately. When simultaneously gave retigabine, ketamine's antidepressant effect in the forced swim test was significantly enhanced with a prolonged effective duration. Together, these results from both male and female mice indicated that adjunctive treatment with retigabine was an alternative to promote the antidepressant effect of ketamine, thus holding the possibility of encountering its possible physical and psychological dependence.