Antidepressant-like effects of ascorbic acid and ketamine involve modulation of GABAA and GABAB receptors

Background it has been suggested that dysregulation of γ-aminobutyric acid (gaba)-mediated neurotransmission is involved in the etiology of major depressive disorder and in the action of the fast-acting antidepressant ketamine. considering that recent evidence has suggested that ascorbic acid may exert an antidepressant-like effect through mechanisms similar to ketamine,this study evaluated the involvement of gabaa and gabab receptors in the antidepressant-like effect of ascorbic acid,comparing the results with those obtained with ketamine. methods to investigate the involvement of gabaa in the antidepressant-like effect of ascorbic acid and ketamine in the tail suspension test (tst),mice were treated with a sub-effective dose of ascorbic acid (0.1 mg/kg,po),ketamine (0.1 mg/kg,ip) or vehicle and 30 minutes later,a sub-effective dose of muscimol (0.1 mg/kg,ip,gabaa receptor agonist) or vehicle was administered. in another set of experiments,mice were treated with ascorbic acid (1 mg/kg,po,active dose in the tst) or vehicle and 30 minutes later,baclofen (1 mg/kg,ip,gabab receptor agonist) was administered. a similar experimental protocol was performed with ketamine (1 mg/kg,ip). results the administration of muscimol combined with ascorbic acid or ketamine produced a synergistic antidepressant-like effect in the tst. moreover,the antidepressant-like effects of ascorbic acid and ketamine were abolished by baclofen. there was no alteration in spontaneous locomotion in any experimental group. conclusions results indicate that the anti-immobility effect of ascorbic acid and ketamine in tst may involve an activation of gabaa receptors and a possible inhibition of gabab receptors. © 2016 institute of pharmacology,polish academy of sciences