The effects of lobeline on depression-like behavior and hippocampal cell proliferation following chronic stress in mice

•Chronic unpredictable stress (CUS) caused depression-like behavior in mice.•Lobeline produced antidepressant-like effects in CUS-exposed mice.•Lobeline increased hippocampal BDNF and cell proliferation in CUS-exposed mice.

We have reported that brain nicotinic acetylcholine receptor (nAChR) ligand lobeline has antidepressant-like effects in mice. The present study examined the effects of lobeline on chronic unpredictable stress (CUS)-induced depression-like behavior, deficits in brain-derived neurotrophic factor (BDNF) expression and cell proliferation in the hippocampus. Adult C57BL/6J mice were exposed to CUS for 6 weeks. Lobeline (1 or 4 mg/kg, s.c.) or saline was administered once daily during the last 14 days of CUS. CUS-exposed mice showed increased immobility time in the FST compared to control. Pretreatment with lobeline (1 mg/kg) significantly reduced immobility time in the CUS-exposed mice. Twenty-four hour following lobeline or saline treatment, BDNF expression or cell proliferation was measured in the hippocampus using Western blotting and bromodeoxyuridine immunohistochemistry, respectively. Lobeline (1 mg/kg) treatment prevented CUS-induced reduction in BDNF expression and cell proliferation in the hippocampus. Overall, our findings suggest that antidepressant-like effects of lobeline could involve nAChR mediated signaling, BDNF expression, and/or hippocampal cell proliferation.