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

Evidence suggests that neuronal nicotinic acetylcholine receptor (nAChR) ligand lobeline has antidepressant-like properties. The present study investigated the effects of lobeline on nicotine withdrawal-induced depression-like behavior. Adult C57BL/6J mice were exposed to nicotine (200 mu g/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 alpha 4 beta 2 nAChR ligand 3-(pyridine-3I-yl)-cytisine on brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-responsive element binding (p-CREB) protein expression in the hippocampus. 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-3I-yl)-cytisine decreased immobility time in the FST and reduced withdrawal-induced increased BDNF and p-CREB expression in the hippocampus. 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.