Retigabine promotes ketamine's antidepressant effect in the forced swim test in male and female C57BL/6J mice.
Pharmacology, biochemistry, and behavior – September 01, 2023
Source: PubMed
Summary
Ketamine shows promise as a rapid antidepressant, but concerns about dependence limit its use. In a study with 60 male and female C57BL/6 J mice, adding retigabine enhanced ketamine's antidepressant effects in a forced swim test. Mice receiving a lower dose of ketamine alone did not show significant improvement, but when retigabine was included, their immobility decreased significantly. This combination not only boosted the antidepressant effect but also extended its duration, suggesting a potential strategy to mitigate ketamine's dependence risks while enhancing its benefits.
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.