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

Abstract

Abstract. 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.

The protective effects of escitalopram on chronic restraint stress-induced memory deficits in adult rats

“…Therefore, stress duration may perturb physiological functions, consequently leading to other associative depression disorders (Chang and Grace, 2014;Yang et al, 2015) and reduction of stress-related locomotor activity (Pechlivanova et al, 2011). There are paradoxical reports on the effects of stress on locomotor activity; for instance, reduction of locomotor activity (Gammoh et al, 2017;Mortazaei et al, 2019), enhancement of locomotor activity (Yang et al, 2015) and no stress-related effects (Duque et al, 2016) are all discussed in various studies. Thus, duration and types of stress, as well as the behavioral assessment methods seem to have affected the locomotor activity results (Schöner et al, 2017).…”

“…Therefore, the optimum dose of escitalopram may have caused more immobility under normal condition and stress conditions. Nevertheless, reduction of locomotor activity due to the application of escitalopram has been reported in both stressful and non-stressful situations (Gammoh et al, 2017). Lin et al (2016) explained that escitalopram administration (10 mg/kg/ day) even under stress conditions did not affect the rodent's motor activity.…”

Valerian and Hops Combination Versus Escitalopram in Models of Depression and Anxiety: A Cross-talk with Oxidative Stress

“…All mice were six to eight weeks old and of an equal ratio of males to females. Animals were kept individually in separate cages in order to reduce anxiety as in (5) Temperature and humidity were controlled at 25°C, 50-60% respectively.…”

“…Group I: control (treated with a single dose of distilled water); group II: valerian-hops (treated with a single dose of 100mg/kg); and group III: Escitalopram (treated with a single dose of 10mg/kg) escitalopram was supplied from Pharma International and the dose selection was made as in (5). After a treatment period of one hour, mice were then subjected to behavioral tests.…”

“…The neurobiology of depression and anxiety is complex and multifactorial. Beyond the well-established monoamine deficiency theory of psychological disorders (4), accumulating evidence points to the role of oxidative stress (5,6). Nitrates, a nitric oxide (NO) metabolite, are a marker of oxidative stress and were shown to increase during acute anxiety (7,8).…”