Antidepressant‐like effects of lobeline in a chronic mild stress model

Abstract

Recently, we have demonstrated that lobeline, a neuronal nicotinic acetylcholine receptor (nAChR) ligand, has antidepressant‐like effects in mice. The objective of the present study was to determine the effects of lobeline in a chronic mild stress (CMS) model. Adult C57BL/6J mice were exposed to CMS for six weeks. Saline or lobeline (1 or 4 mg/kg, s.c.) were administered once daily during the last two weeks of CMS. Compared to unstressed group, mice exposed to CMS showed increased immobility time in forced swim test, a measure for depression‐like behavior, which was reversed by chronic lobeline treatment (unstressed: 256 ± 8, CMS: 385 ± 24, CMS + lobeline 1 mg/kg: 213 ± 39, CMS + lobeline 4 mg/kg: 266 ± 19 sec). Mice were sacrificed 24 h after chronic treatment to determine brain‐derived neurotrophic factor (BDNF) expression in hippocampus and prefrontal cortex. CMS significantly (p < 0.05) reduced BDNF expression in hippocampus which was reversed by chronic treatment with 1 mg/kg lobeline (CMS: 60 ± 13%, CMS + lobeline 1 mg/kg: 141 ± 12% of unstressed group). However, BDNF expression in prefrontal cortex was not changed by CMS or drug treatment. Overall, the results indicate that lobeline has antidepressant‐like effects likely involving nAChR signaling and regulation of BDNF expression in hippocampus. (Supported in part by SDSURF‐JRF)