AR-R 17779 improves social recognition in rats by activation of nicotinic alpha7 receptors

Psychopharmacology (Berl). 2004 Apr;172(4):375-83. doi: 10.1007/s00213-003-1668-7. Epub 2004 Jan 15.


Rationale: Nicotine and agonists at alpha(4)beta(2) and alpha(7) nicotinic acetylcholine receptors (nAChRs) improve learning and memory. The alpha(7)-nAChR subtype is of special interest, since it appears to play no role in the abuse liability of nicotine.

Objectives and methods: To further investigate the role of the alpha(7)-nAChR in learning and memory, the effects of the specific alpha(7)-nAChR agonist AR-R17779 on cognition were measured in the rat social recognition test (SRT) and the effect of the alpha(7)-nAChR antagonist methyllycaconitine (MLA) was studied. The SRT and a scopolamine-induced deficit version were validated with the acetylcholinesterase inhibitor metrifonate. Social memory was measured by the ability of an adult rat to recognize a juvenile rat after a delay. The difference in social interaction time (SIT) was measured between two encounters. The difference in SIT is expressed as percent reduction in social interaction time (%RSIT).

Results: Metrifonate (10 and 30 mg/kg PO) increased %RSIT in a behaviorally specific manner, employing a 24-h interval and reversed the scopolamine-induced deficit at a retention time of 15 min. Likewise, AR-R17779 increased %RSIT in unimpaired animals (1, 3, 10 and 30 mg/kg SC) employing a 24-h retention interval, and reversed the scopolamine-induced deficit (0.3 and 1 mg/kg SC) after a 15-min retention interval. The effects of AR-R17779 (1 mg/kg SC) in unimpaired animals were reversed by MLA (10 micro g ICV), which induced a decrease of %RSI at a 15-min retention interval when given alone.

Conclusions: AR-R17779 increased social recognition memory by activation of alpha(7)-nAChRs, suggesting that alpha(7)-nAChR agonists possess cognitive-enhancing properties.

Publication types

  • Comparative Study

MeSH terms

  • Aconitine / administration & dosage
  • Aconitine / analogs & derivatives*
  • Aconitine / pharmacology
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects
  • Bridged-Ring Compounds / administration & dosage
  • Bridged-Ring Compounds / pharmacology*
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Male
  • Maze Learning / drug effects
  • Neurons / metabolism
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Antagonists / administration & dosage
  • Nicotinic Antagonists / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic / biosynthesis
  • Receptors, Nicotinic / drug effects*
  • Recognition, Psychology / drug effects*
  • Social Behavior*
  • Spiro Compounds / administration & dosage
  • Spiro Compounds / pharmacology*
  • Trichlorfon / administration & dosage
  • Trichlorfon / pharmacology
  • alpha7 Nicotinic Acetylcholine Receptor


  • AR-R 17779
  • Bridged-Ring Compounds
  • Cholinesterase Inhibitors
  • Chrna7 protein, rat
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Spiro Compounds
  • alpha7 Nicotinic Acetylcholine Receptor
  • methyllycaconitine
  • Trichlorfon
  • Aconitine