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.