Van Kampen Marja, Selbach Karin, Schneider Renate, Schiegel Elleonore, Boess Frank, Schreiber Rudy
CNS Research, Bayer AG, 42096 Wuppertal, Germany.
Psychopharmacology (Berl). 2004 Apr;172(4):375-83. doi: 10.1007/s00213-003-1668-7. Epub 2004 Jan 15.
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.
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).
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.
AR-R17779 increased social recognition memory by activation of alpha(7)-nAChRs, suggesting that alpha(7)-nAChR agonists possess cognitive-enhancing properties.
尼古丁以及α4β2和α7烟碱型乙酰胆碱受体（nAChRs）的激动剂可改善学习和记忆。α7 - nAChR亚型特别引人关注，因为它似乎在尼古丁的成瘾性方面不起作用。
为了进一步研究α7 - nAChR在学习和记忆中的作用，在大鼠社会识别试验（SRT）中测量了特异性α7 - nAChR激动剂AR - R17779对认知的影响，并研究了α7 - nAChR拮抗剂甲基lycaconitine（MLA）的作用。用乙酰胆碱酯酶抑制剂美曲膦酯验证了SRT和东莨菪碱诱导的缺陷版本。通过成年大鼠在延迟后识别幼年大鼠的能力来测量社会记忆。测量两次相遇之间的社会互动时间（SIT）差异。SIT差异表示为社会互动时间减少百分比（%RSIT）。
美曲膦酯（10和30mg/kg口服）以行为特异性方式增加%RSIT，采用24小时间隔，并在15分钟的保留时间逆转了东莨菪碱诱导的缺陷。同样，AR - R17779在未受损动物（1、3、10和30mg/kg皮下注射）中采用24小时保留间隔增加了%RSIT，并在15分钟保留间隔后逆转了东莨菪碱诱导的缺陷（0.3和1mg/kg皮下注射）。AR - R17779（1mg/kg皮下注射）对未受损动物的作用被MLA（10μg脑室内注射）逆转，MLA单独给药时在15分钟保留间隔诱导%RSI降低。
AR - R17779通过激活α7 - nAChRs增加社会识别记忆，表明α7 - nAChR激动剂具有认知增强特性。
