Neuronal nicotinic receptor antagonist reduces anxiety-like behavior in mice

Neurosci Lett. 2011 Oct 31;504(3):237-41. doi: 10.1016/j.neulet.2011.09.035. Epub 2011 Sep 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacokinetics
  • Anti-Anxiety Agents / pharmacology
  • Anti-Anxiety Agents / therapeutic use*
  • Anxiety / drug therapy*
  • Blood-Brain Barrier
  • Brain / drug effects
  • Exploratory Behavior / drug effects
  • Hexamethonium / pharmacokinetics
  • Hexamethonium / therapeutic use
  • Lobeline / pharmacokinetics
  • Lobeline / therapeutic use*
  • Mecamylamine / pharmacokinetics
  • Mecamylamine / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Nicotinic Agonists / pharmacokinetics
  • Nicotinic Agonists / therapeutic use*
  • Nicotinic Antagonists / pharmacokinetics
  • Nicotinic Antagonists / therapeutic use*
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / physiology

Substances

  • Anti-Anxiety Agents
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • alpha(4)beta(4) nicotinic receptor
  • nicotinic receptor alpha3beta2
  • nicotinic receptor alpha4beta2
  • Hexamethonium
  • Mecamylamine
  • Lobeline