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 (3.35 mg/kg, t.i.d.) from days 1 to 7 and alongside lacidipine (0.3, 1, and 3 mg/kg, i.p.) given from days 1 to 14. Somatic withdrawal signs were noted 48 h after last dose of nicotine. Bay-K8644 (LTCC agonist) was administered in mice subjected to nicotine-withdrawal and lacidipine (3 mg/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 3 mg/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.
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Abbreviations
- ANOVA:
-
Analysis of variance
- b.w. :
-
Body weight
- CAT:
-
Catalase
- DA:
-
Dopamine
- EPM:
-
Elevated plus maze
- GABA:
-
Gamma amino butyric acid
- GSH:
-
Glutathione
- i.p. :
-
Intraperitoneal
- LCD:
-
Lacidipine
- LTCCs:
-
L-type voltage-dependent Ca2+ channels
- MDA:
-
Malondialdehyde
- NAc:
-
Nucleus accumbens
- nAChRs:
-
Nicotinic cholinergic receptors
- Nic:
-
Nicotine
- O.D.:
-
Optical density
- ROS:
-
Reactive oxygen species
- s.c. :
-
Subcutaneous
- SOD:
-
Superoxide dismutase
- t.i.d. :
-
Ter in die (3 times a day)
- TBARS:
-
Thiobarbituric acid reactive substances
- TL:
-
Transfer latency
- TST:
-
Tail suspension test
- VTA:
-
Ventral tegmentum
- λ max :
-
Maximum wavelength
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Acknowledgements
The authors are thankful to I. K. Gujral Punjab Technical University, Kapurthala (Punjab) and the management of A.S.B.A.S.J.S.M. College of Pharmacy, Bela (Ropar), for providing necessary research facilities.
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NB conceived and designed this study. KK performed the research. MK analyzed the data, drafted the original, and revised manuscript. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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This study was approved by the “Institutional Animal Ethics Committee (IAEC)” of the A.S.B.A.S.J.S.M. College of Pharmacy, Bela (Ropar), vide protocol no. ASCB/IAEC/08/15/108 (dated: 28-11-2015). The guidelines of “The Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA),” Ministry of Forests and Environment, and Government of India (New Delhi) were followed for all animal experiments and care of animals.
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Khurana, K., Kumar, M. & Bansal, N. Lacidipine Attenuates Symptoms of Nicotine Withdrawal in Mice. Neurotox Res 39, 1920–1936 (2021). https://doi.org/10.1007/s12640-021-00421-2
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DOI: https://doi.org/10.1007/s12640-021-00421-2