Lacidipine attenuates caffeine-induced anxiety-like symptoms in mice: Role of calcium-induced oxido-nitrosative stress

Abstract

Background: Anxiety is a disorder of multi-factorial pathogenesis involving interrelated pathways of neurotransmitters, oxidative stress and metamorphosed calcium-signaling that negatively affects brain functions. Modulation of Ca²⁺-channels outlines a promising strategy to curb the progression of anxiety-like disorders through attenuation of redox-imbalance. The current research scheme was designed to explore the anxiolytic effects of lacidipine (L-type Ca²⁺-channel blocker; LCD) pretreatment in caffeine-induced anxiety-like symptom model in mice.

Methods: Forty-two Swiss albino mice (25-30 g) were distributed to 7 groups (n = 6): Vehicle control, caffeine, alprazolam + caffeine, lacidipine(0.3, 1 and 3 mg/kg, ip)+caffeine and Bay-K8644+LCD(3)+caffeine. Caffeine (25 mg/kg, ip) was administered from day 8 to 14 to induce anxiety-like symptoms in mice. Lacidipine (0.3, 1 and 3 mg/kg, ip) and alprazolam (0.25 mg/kg, ip) were administered from day 1 to 14 in separate groups. Bay-K8644 (Ca²⁺-channel agonist) was injected on day 14 to delineate the role of Ca²⁺ in anti-anxiety effect of LCD in caffeine-treated mice. Elevated zero maze and mirror chamber test were employed to assess anxiety-like behavior. Afterwards, the mice were sacrificed and whole brains were harvested for estimation of biomarkers of oxido-nitrosative stress, such as TBARS, GSH, SOD, catalase and total nitrite content.

Results: An increase in brain oxido-nitrosative stress and anxiety-like behavior was observed in caffeine treated mice. LCD pretreatment attenuated the brain oxido-nitrosative stress and anxiety-like behavior in mice in caffeine treated mice. Anxiolytic effect of LCD was attenuated by Bay-K8644 (0.5 mg/kg) in caffeine treated mice.

Conclusion: LCD (L-type Ca²⁺-channel antagonist) pretreatment attenuated caffeine-induced oxido-nitrosative stress and anxiety-like behavior.

Keywords: Anxiety; Calcium channel; Lacidipine; Nitrite; Oxidative stress.