Neuronal nicotinic receptor antagonist reduces anxiety-like behavior in mice

Brain cholinergic neurotransmission has been implicated in the modulation of anxiety in humans and evidence suggests that drugs targeting neuronal nicotinic acetylcholine receptor (nAChR) could have potential for the treatment of anxiety. The objective of present study was to examine anxiolytic effects of lobeline (0.04 or 0.1 mg/kg), a nAChR antagonist, in C57BL/6J mice using elevated plus-maze (EPM) and marble-burying test. Lobeline (0.04 mg/kg) significantly increased open arm time on EPM and reduced number of marbles buried. Similarly, mecamylamine (0.3 mg/kg) produced anxiolytic effects, while peripherally acting hexamethonium (0.3 mg/kg) failed to produce any response. These results provide evidence that lobeline has anxiolytic potential and nAChR antagonists may represent a new class of anxiolytics in humans.

► Lobeline (0.04 mg/kg) treatment produced anxiolytic-like effects in mice.
► Mecamylamine (0.3 mg/kg) treatment produced anxiolytic-like effects in mice.
► Hexamethonium (0.3 mg/kg) treatment did not produce anxiolytic-like effects.
► Centrally acting nicotinic ligands could be new class of anxiolytics.