Evidence for the Involvement of Potassium Channel Inhibition in the Antidepressant-Like Effects of Hesperidin in the Tail Suspension Test in Mice

Abstract

The administration of hesperidin elicits an antidepressant-like effect in mice by a mechanism dependent on an interaction with the l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, whose stimulation is associated with the activation of potassium (K + ) channels. Thus, this study investigated the involvement of different types of K + channels in the antidepressant-like effect of hesperidin in the mice tail suspension test (TST). The intracerebroventricular administration of tetraethylammonium (TEA, a nonspecific blocker of K + channels), glibenclamide (an ATP-sensitive K + channel blocker), charybdotoxin (a large-and intermediate-conductance calcium-activated K + channel blocker) or apamin (a small-conductance calcium-activated K + channel blocker) combined with a subeffective dose of hesperidin (0.01 mg/kg, intraperitoneally [i.p.]) was able to produce a synergistic antidepressant-like effect in the mice TST. Moreover, the antidepressant-like effect elicited by an effective dose of hesperidin (0.3 mg/kg, i.p.) in TST was abolished by the treatment of mice with pharmacological compounds K + channel openers (cromakalim and minoxidil). Results showed that the antidepressantlike effect of hesperidin in TST may involve, at least in part, the modulation of neuronal excitability through inhibition of K + channels and may act through a mechanism dependent on the inhibition of l-arginine-NO pathway.

Agonist and Antagonist Effects of ATP-Dependent Potassium Channel on Penicillin Induced Epilepsy in Rats

“…Made with ATP-sensitive K + channel openers like diazoxide and cromakalim in vivo and in vitro experiments antiepileptic effects of these substances are shown 13,20 . Similar results were obtained from some performed studies 21,22 . Potassium channel openers, as a result of membrane hyperpolarization, reduce neuronal excitability.…”

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice

“…Furthermore, our recent study suggests that psychological stress-induced depression-like behaviors in mice were mitigated by treatment with kososan, but not the antidepressant milnacipran [ 31 ], a serotonin-noradrenaline reuptake inhibitor. Besides, many rodent studies have shown that some compounds (e.g., apigenin [ 32 , 33 ], caffeic acid [ 34 ], perillaldehyde [ 35 , 36 ], and rosmarinic acid [ 37 ] contained in Perillae Herba; hesperidin [ 38 , 39 ] and nobiletin [ 40 , 41 ] contained in Aurantii Nobilis Pericarpium) exert antidepressant-like effects. Although there is increasing evidence for kososan’s therapeutic benefits for depression-like behaviors in preclinical studies, little is known about the efficacy of kososan in the behavioral abnormalities caused by CSDS as an animal model of psychosocial stress.…”

Potentiation of Antidepressant Effects of Agomelatine and Bupropion by Hesperidin in Mice

“…The combination of hesperidin with agomelatine may help in reducing side/adverse effects of later drug. Though previous reports suggest no impact on locomotion of hesperidin [ 41 ], agomelatine [ 42 ], and bupropion [ 43 ] treatments, the drawback of present study is not considering the evaluation of locomotor activity along with immobility testing. Additional parameters such as BDNF, glutamate, and melatonin should be further investigated in different preclinical and clinical settings as a future endeavour.…”