Chlorpheniramine and escitalopram: Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety

There is a crosstalk between mood disorders and oxidative stress. Chlorpheniramine (CPA), a first generation antihistamine, is hypothesized to have an anxiolytic role at high doses; however, its antidepressant and antioxidant roles have not previously been investigated. The aim of the current study was to evaluate the antidepressant and anxiolytic effects of CPA treatment in association with nitric oxide (NO) and super oxide dismutase (SOD) activity in a mouse model of anxiety. BALB/c mice were divided into unstressed (naïve), control, and CPA- (0.5 mg/kg) and escitalopram- (ESC; 10 mg/kg) treated groups for 3 weeks. Subsequently, they were immobilized for 6 h and subjected to behavioural paradigms as follows: The open field test, the elevated plus maze (EPM) and the forced swim test to investigate motor function, anxiety and depression, respectively. The mice were sacrificed and serum was obtained to detect NO and SOD activity. Compared with the control group, the CPA-treated group demonstrated an antidepressant effect similar to that of the ESC-treated group. In addition, CPA prevented stress-induced NO without affecting SOD activity. CPA did not improve anxiety-like behaviour in the EPM, nor did it improve stress-induced locomotion and rearing, as demonstrated by the OFT. Thus, to the best of our knowledge, this is the first study to evaluate the antidepressant role of CPA in association with NO metabolism. However, further studies are required to elucidate the underlying mechanism.