Inhibition of potassium sensitive adenosine triphosphate channels potentiates anti-depressant activity of creatine in mice

Background: Depression is a mood disorder with poorly understood aetiology and treatment outcomes. Treatment with creatine, a nutraceutical associated with potassium sensitive adenosine triphosphate channels (KATP), produced improved results in preclinical studies of depression.

Objective: This study sought to investigate the role of KATP inhibitor and activator on the antidepressant activity of creatine in mice.

Methods: Four hundred and ninety male mice randomly allotted into groups of seven were either untreated (naïve) or pretreated with effective or sub-effective doses of glibenclamide or cromakalim, followed by selected doses of creatine, amitriptyline or imipramine for fourteen consecutive days. Groups of naïve and treated animals were thereafter subjected to forced swim test (FST) or tail suspension test (TST) or open field test (OFT).

Results: Pretreatment with effective or subeffective doses of glibenclamide and creatine, imipramine or amitriptyline significantly (p<0.05) reduced duration of immobility in the TST and FST. Conversely, cromakalim administered in combination with creatine, imipramine and amitriptyline antagonized the antidepressant effect of creatine, imipramine and amitriptyline. However, there was no difference in locomotor activity in the OFT across the treatment groups.

Conclusion: Inhibition of KATP channels potentiates the antidepressant activity of creatine.