Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice

Neuropharmacology. 2007 Apr;52(5):1256-62. doi: 10.1016/j.neuropharm.2007.01.006. Epub 2007 Jan 20.


The nicotine in tobacco is thought to modulate neuronal systems regulating mood. Moreover, it appears possible that blockade rather than activation of beta2-containing (beta2*) nicotinic acetylcholine receptors (nAChRs) may lead to antidepressant-like effects. We used cytisine, a partial agonist of alpha4/beta2*nAChRs and a full agonist at alpha3/beta4*nAChRs, in several tests of antidepressant efficacy. Further, we used c-fos expression to identify potential neurobiological correlates of the antidepressant-like effects of cytisine. Cytisine had antidepressant-like effects in several animal models of antidepressant efficacy. In addition, immunohistochemical analyses indicated that cytisine could reduce c-fos immunoreactivity in the basolateral amygdala by approximately 50%. These data show that cytisine acts like classical antidepressants in rodent models of antidepressant efficacy. In addition, cytisine's ability to block alpha4/beta2*nAChRs may be responsible for its antidepressant-like properties, and these may be mediated through a reduction of neuronal activity in the basolateral amygdala. These studies also suggest that both antagonists and partial agonists of alpha4/beta2*nAChRs would be interesting targets for the development of novel antidepressant drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Antidepressive Agents*
  • Anxiety / psychology
  • Azocines / pharmacology
  • Brain / pathology
  • Depression / pathology*
  • Depression / psychology*
  • Feeding Behavior / drug effects
  • Gene Expression / drug effects
  • Genes, fos / drug effects
  • Hindlimb Suspension / psychology
  • Immunohistochemistry
  • Male
  • Mecamylamine / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Nicotinic Agonists / pharmacology*
  • Quinolizines / pharmacology
  • Receptors, Muscarinic / drug effects*
  • Swimming / psychology


  • Alkaloids
  • Antidepressive Agents
  • Azocines
  • Nicotinic Agonists
  • Quinolizines
  • Receptors, Muscarinic
  • cytisine
  • Mecamylamine