Combination therapy with citalopram, bupropion, and lithium for the amelioration of the depressive-related effects induced by dexamethasone in male mice.

Combination therapy is a proposed strategy in the treatment of depression. Therefore, this research was designed to evaluate the effects of drug combinations of citalopram, bupropion, and lithium on depression-related behaviors induced by dexamethasone (DEX) and aimed to detect the type of interaction among components. Depression-related behaviors were assessed by forced swim test (FST) and tail suspension test (TST), as well as locomotor activity, was assessed using an open-field test (OFT) in male mice. Our results revealed that 24 h after DEX (8 mg/kg; intraperitoneally (i.p.)) administration, the immobility time of the FST and TST increased, proposing a depressive-related behavior. Moreover, 24 h after DEX administration, the number of the CA1 dark cells enhanced, and the level of plasma corticosterone, the primary glucocorticoid in mice, declined. I.p. administrations of lithium (8 mg/kg), bupropion (8 mg/kg) or citalopram (8 mg/kg) diminished the depression-related behaviors induced by DEX via reduction of immobility time in the FST and TST without affecting the locomotor activity, showing an antidepressant-related effect. All two-drug combinations, at subthreshold dosages, exerted antidepressive-related responses. Isobolographic analysis indicated synergistic antidepressant-related effects of citalopram plus bupropion, citalopram plus lithium, as well as bupropion plus lithium. These results suggest synergistic antidepressant-related behaviors of citalopram plus bupropion, citalopram plus lithium, as well as bupropion plus lithium on the amelioration of the depressive-related effects induced by DEX. Combination therapy with citalopram, bupropion, and lithium might be a novel therapeutic approach for depression treatment. However, additional investigations are needed to clarify the exact interactions between components.