Nicotinic Antagonist UFR2709 Inhibits Nicotine Reward and Decreases Anxiety in Zebrafish

Molecules. 2020 Jun 30;25(13):2998. doi: 10.3390/molecules25132998.


Zebrafish is becoming a popular animal model in neuropharmacology and drug discovery, mainly due to its ease of handling and low costs involved in maintenance and experimental work. This animal displays a series of complex behaviours that makes it useful for assessing the effects of psychoactive drugs. Here, adult zebrafish were used for assessment of the anxiolytic and anti-addictive properties of UFR2709, a nicotinic receptor (nAChR) antagonist, using two behavioural paradigms to test for addiction, the novel tank diving test to assess anxiety and the conditioned place preference (CPP). Furthermore, the expression of nAChR subunits α4 and α7 was measured in the zebrafish brain. The results show that UFR2709 exhibits an anxiolytic effect on zebrafish and blocks the effect evoked by nicotine on CPP. Moreover, UFR2709 significantly decreased the expression of α4 nicotinic receptor subunit. This indicates that UFR2709 might be a useful drug for the treatment of nicotine addiction.

Keywords: anxiety; conditioned place preference (CPP); nicotinic receptor; novel tank test (NTT); reward; zebrafish.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anxiety / chemically induced
  • Anxiety / prevention & control*
  • Behavior, Animal / drug effects*
  • Benzoates / pharmacology*
  • Disease Models, Animal
  • Nicotine / administration & dosage
  • Nicotine / antagonists & inhibitors*
  • Nicotinic Antagonists / pharmacology*
  • Pyrrolidines / pharmacology*
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Reward*
  • Swimming
  • Zebrafish


  • Anti-Anxiety Agents
  • Benzoates
  • Nicotinic Antagonists
  • Pyrrolidines
  • Receptors, Nicotinic
  • UFR2709
  • nicotinic acetylcholine receptor alpha4 subunit
  • Nicotine