Lamirault L, Simon H
Laboratoire de Neuropsychobiologie des Désadaptations, CNRS UMR 5541, Université Victor Segalen Bordeaux 2, BP 31, 146, rue Léo Saignat, 33076 Cedex, Bordeaux, France.
Neuropharmacology. 2001 Dec;41(7):844-53. doi: 10.1016/s0028-3908(01)00123-x.
There is recent evidence that activation of central 5-hydroxytryptamine (5-HT)4 receptors enhances cognitive processes such as learning and memory. In the present study, we assessed the effects of a selective 5-HT4 receptors agonist, RS 67333 [1(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-butyl-4-piperidinyl)-1-propanone], in a two-trial recognition task designed to test place or object recognition memory.RS 67333 was injected in young adult (0.0001, 0.01, 1 mg/kg, i.p.) and old (0.0001, 0.01, 1, 10 mg/kg, i.p.) rats before the acquisition phase, immediately after it, or before the retrieval phase, to determine the stage of information processing affected by the compound. When injected before the acquisition phase, RS 67333 (1 mg/kg) enhanced place and object recognition in young adult rats. In old rats, RS 67333 (10 mg/kg) improved place recognition when injected before the acquisition phase, and object recognition when injected before the acquisition or in the consolidation phase of information processing. The beneficial effects of RS 67333 were abolished by prior treatment with a selective 5-HT4 receptors antagonist, GR 125487 [(1-[2-[methyl sulphonyl)-amino]ethyl]-4-piperidinyl-methyl 5-fluoro-2-methoxy-1H-indole-3-carboxylate); 10 mg/kg, i.p.]. These results support the view that selective 5-HT4 receptors agonists may be of value in the treatment of cognitive disorders related to normal aging or neurodegenerative conditions such as Alzheimer's disease.
最近有证据表明，中枢5-羟色胺（5-HT）4受体的激活可增强学习和记忆等认知过程。在本研究中，我们在一项旨在测试位置或物体识别记忆的双试验识别任务中，评估了选择性5-HT4受体激动剂RS 67333[1-(4-氨基-5-氯-2-甲氧基苯基)-3-(1-正丁基-4-哌啶基)-1-丙酮]的作用。在获取阶段之前、之后或检索阶段之前，将RS 67333注射到年轻成年大鼠（0.0001、0.01、1mg/kg，腹腔注射）和老年大鼠（0.0001、0.01、1、10mg/kg，腹腔注射）体内，以确定该化合物影响信息处理的阶段。在获取阶段之前注射时，RS 67333（1mg/kg）可增强年轻成年大鼠的位置和物体识别能力。在老年大鼠中，RS 67333（10mg/kg）在获取阶段之前注射时可改善位置识别能力，在获取阶段之前或信息处理的巩固阶段注射时可改善物体识别能力。预先用选择性5-HT4受体拮抗剂GR 125487[(1-[2-(甲基磺酰基)-氨基]乙基]-4-哌啶基-甲基5-氟-2-甲氧基-1H-吲哚-3-羧酸酯；10mg/kg，腹腔注射)治疗可消除RS 67333的有益作用。这些结果支持以下观点，即选择性5-HT4受体激动剂可能对治疗与正常衰老或神经退行性疾病（如阿尔茨海默病）相关的认知障碍有价值。
