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


OBJECTIVE
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.
Van Kampen
Marja
M
CNS Research, Bayer AG, 42096 Wuppertal, Germany.
Selbach
Karin
K
Schneider
Renate
R
Schiegel
Elleonore
E
Boess
Frank
F
Schreiber
Rudy
R
D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000187:drug effects*; D021641:Recognition, Psychology / Q000187:drug effects*; D012919:Social Behavior; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D014236:Trichlorfon / Q000008:administration & dosage / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor
C408128:AR-R 17779; D001952:Bridged-Ring Compounds; D002800:Cholinesterase Inhibitors; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D013141:Spiro Compounds; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D014236:Trichlorfon; D000157:Aconitine