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The effects of lobeline on nicotine withdrawal-induced depression-like behavior in mice

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Abstract

Rationale

Evidence suggests that neuronal nicotinic acetylcholine receptor (nAChR) ligand lobeline has antidepressant-like properties.

Objectives

The present study investigated the effects of lobeline on nicotine withdrawal-induced depression-like behavior.

Methods

Adult C57BL/6J mice were exposed to nicotine (200 μg/ml) in drinking solution for 3 weeks. During withdrawal, depression-like behavior was measured by the forced swim test (FST). We also determined norepinephrine (NE) levels in the prefrontal cortex (PFC) and hippocampus during nicotine withdrawal. Furthermore, we determined the effects of repeated treatment with lobeline or a selective α4β2 nAChR ligand 3-(pyridine-3́-yl)-cytisine on brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-responsive element binding (p-CREB) protein expression in the hippocampus.

Results

Withdrawal from chronic nicotine increased immobility time in the FST, a measure for depression-like behavior. Pretreatment with lobeline significantly decreased immobility time during nicotine withdrawal. In addition, pretreatment with lobeline attenuated nicotine withdrawal-induced increased NE levels in the PFC and hippocampus. Further, repeated treatment with lobeline or 3-(pyridine-3́-yl)-cytisine decreased immobility time in the FST and reduced withdrawal-induced increased BDNF and p-CREB expression in the hippocampus.

Conclusions

Taken together, our results indicate that lobeline attenuated nicotine withdrawal-induced depression-like behavior likely by targeting brain nAChRs, noradrenergic neurotransmission, and/or hippocampal BDNF. Thus, lobeline may have some potential to prevent smoking relapse by counteracting nicotine withdrawal-induced depression in humans.

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Acknowledgments

The authors wish to thank Dr. Chandradhar Dwivedi and Dr. Ruth Guillermo for their help in Western blot studies. The anti-β-tubulin antibody developed by Dr. Michael Klymkowsky was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biology, Iowa City, IA 52242. This study was supported in part by the funds from the College of Pharmacy and grants from SDSU Research Foundation and RSSF (SR). All experiments were in compliance with the National Institutes of Health guidelines for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at South Dakota State University in the USA.

Conflict of interest

The authors declare that there is no conflict of interest related to this study.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Avera Health and Science Center, SAV 265, Brookings, SD, 57007, USA

    Monzurul Amin Roni & Shafiqur Rahman

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  1. Monzurul Amin Roni
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  2. Shafiqur Rahman
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Correspondence to Shafiqur Rahman.

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Roni, M.A., Rahman, S. The effects of lobeline on nicotine withdrawal-induced depression-like behavior in mice. Psychopharmacology 231, 2989–2998 (2014). https://doi.org/10.1007/s00213-014-3472-y

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  • DOI: https://doi.org/10.1007/s00213-014-3472-y

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