Abstract
Nicotine-withdrawal after daily exposure manifests somatic and affective symptom including a range of cognitive deficits. Earlier studies suggested participation of L-type calcium channels (LTCCs) in development of nicotine dependence and expression of withdrawal signs. An upsurge in Ca2+-induced oxidative stress in brain underlies the biochemical events and behavioral signs of nicotine-withdrawal. The present study is aimed to explore the effects of lacidipine (LTCC antagonist) against nicotine-withdrawal. Swiss albino mice were administered ( -)-nicotine hydrogen tartrate (3.35mg/kg, t.i.d.) from days 1 to 7 and alongside lacidipine (0.3, 1, and 3mg/kg, i.p.) given from days 1 to 14. Somatic withdrawal signs were noted 48h after last dose of nicotine. Bay-K8644 (LTCC agonist) was administered in mice subjected to nicotine-withdrawal and lacidipine (3mg/kg) treatments. Behavioral tests of memory, anxiety, and depression were conducted on days 13 and 14 to assess the effects of lacidipine on affective symptoms of nicotine-withdrawal. Biomarkers of oxido-nitrosative were quantified in the whole brain. Nicotine-withdrawal significantly enhanced somatic signs and symptoms of anxiety, depression, and memory impairment in mice. Lacidipine (1 and 3mg/kg) attenuated nicotine-withdrawal induced somatic symptoms and also ameliorated behavioral abnormalities. Nicotine-withdrawal triggered an upsurge in brain lipid peroxidation, total nitrite content, and decline in antioxidants, and these effects were attenuated by lacidipine. Bay-K8644 significantly abolished improvement in somatic and affective symptoms, and antioxidant effects by lacidipine in mice subjected to nicotine-withdrawal. Lacidipine mitigated nicotine-withdrawal triggered somatic and affective symptoms owing to decrease in brain oxido-nitrosative stress.
Highlights
Nicotine is identified as the major factor contributing to tobacco dependence
No significant change in somatic withdrawal signs was observed in mice that were injected lacidipine per se (3 mg/kg) and mice subjected to vehicle treatments
The development, expression, and progress of nicotine-withdrawal signs have been associated with different subtypes of L-type calcium channels (LTCCs) (Katsura et al 2002; Liu et al 2017; Bernardi et al 2014) that prompted to use of LCD treatment protocol along with the nicotine-withdrawal paradigm in the current study
Summary
Multiple attempts to quit tobacco consumption with high relapse rates are linked with nicotine dependence (Fowler and Kenny 2014). Small doses of nicotine or tobacco consumption are often associated with relief in stress (Holliday and Gould 2016), pain (Ditre et al 2016; Ditre et al 2011), and symptoms of anxiety (Morissette et al 2007; File et al 1998). With repeated exposure, tolerance develops to some of the behavioral effects of nicotine (Benowitz 2009; Mishra et al 2015). Nicotine abstinence manifests withdrawal symptoms (somatic, affective, and cognitive) such as tremors, decreased heart rate, discomfort in the gastrointestinal tract, appetite exacerbation, hyperalgesia, anhedonia, dysphoria, irritability, and a range of behavioral changes (e.g., anxiety, loss of memory, depression) (Foll and Goldberg 2009; Cohen and George 2013)
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