A shea butter-based ketamine ointment :|the ameliorative effects of transdermal ketamine on behavioral despair

Abstract

After a decade of monoaminergic antidepressants, repurposing ketamine in depression launched a new era with its rapid-onset nature and unique action mechanism based on glutamatergic neuroplasticity. Ketamine and its enantiomers were delivered by common enteral and parenteral routes with the disadvantages of first-pass effect, relatively low bioavailability, rapid plasma fluctuations, or inconvenience. The combination of ketamine and transdermal delivery is a worthy choice to overcome most of these disadvantages with steady plasma concentrations and bypassing the gastrointestinal tract. Transdermal ketamine has been used for pain therapy and recently gained attention for its use with different types of depression. In order to offer a user-friendly alternative for depression, the present study aimed to assess the behavioral results of 2-day ketamine ointment treatment in the rodent model of depression, behavioral despair. Naïve14 adult male Wistar rats were grouped as the ketamine and vehicle groups which received a shea butter-based 5% w/w ketamine ointment and drug-free vehicle, respectively for 2 days twice daily on shaved dorsal backs. The ketamine group showed significantly lower immobility scores in the Forced Swim Test (FST) compared to the vehicle group. The locomotor activity and anxiety levels were similar for both groups assessed through the Open Field Test (OFT) and Elevated Plus Maze (EPM). Our results demonstrated that 2- day ketamine ointment treatment produces an antidepressant effect without causing an increase in the general locomotor activity or a change in anxiety levels. Ketamine with its chemically ideal nature for transdermal delivery may offer a potent therapeutic response as an alternative for traditional antidepressants.