Freret Thomas, Paizanis Eleni, Beaudet Gregory, Gusmao-Montaigne Andreia, Nee Gerald, Dauphin François, Bouet Valentine, Boulouard Michel
Groupe Mémoire et Plasticité Comportementale (GMPc) EA 4259, Université de Caen Basse-Normandie, Campus Horowitz, Bd Becquerel, 14032, Caen Cedex, France,
Psychopharmacology (Berl). 2014 Jan;231(2):393-400. doi: 10.1007/s00213-013-3247-x. Epub 2013 Aug 31.
Recent data suggest that 5-HT7 receptors (5-HT7R) are involved in memory processes and, particularly, those related to novelty-induced arousal, even though this remains so far speculative and controversial. In order to assess the role of 5-HT7R in episodic-like memory, mice were administered 5-carboxamidotryptamine (5-CT, a 5-HT1A/1B/1D/7R agonist) and/or SB-269970 (a selective 5-HT7R antagonist) immediately after the acquisition session of the novel object recognition test.
The object recognition test was performed in order to assess the effects of modulation of 5-HT7R during consolidation phase on episodic-like memory performances in mice. A protocol including 3 days of familiarisation to the apparatus has been realised in order to decrease the effect of novelty-induced arousal.
With a 2-h delay, SB-269970 (3 and 10 mg/kg, administered subcutaneously) impaired the discrimination of the novel object. With a 4-h delay, while control mice were not able to discriminate the novel object, mice treated with 5-CT (1 mg/kg) showed a significant discrimination. This promnesic effect with a long delay is effectively mediated by 5-HT7R activation since it was blocked by SB-269970 (10 mg/kg), but not by WAY-100135 (10 mg/kg) or by GR-127935 (10 mg/kg).
These data suggest that 5-HT7R tonically modulates cognitive processes involved in consolidation performances in object recognition. Therefore, 5-HT7R could be a promising target to treat memory dysfunctions (especially episodically related deficits) related to normal or pathological ageing.
近期数据表明，5-羟色胺7型受体（5-HT7R）参与记忆过程，尤其是与新奇性诱导的觉醒相关的记忆过程，尽管目前这一观点仍具有推测性且存在争议。为了评估5-HT7R在情景样记忆中的作用，在新颖物体识别测试的习得阶段后，立即给小鼠注射5-羧基酰胺色胺（5-CT，一种5-HT1A/1B/1D/7R激动剂）和/或SB-269970（一种选择性5-HT7R拮抗剂）。
进行物体识别测试，以评估在巩固阶段调节5-HT7R对小鼠情景样记忆表现的影响。为了减少新奇性诱导的觉醒的影响，实施了一个包括3天熟悉实验装置的方案。
延迟2小时后，皮下注射3毫克/千克和10毫克/千克的SB-269970损害了对新奇物体的辨别能力。延迟4小时后，虽然对照小鼠无法辨别新奇物体，但注射1毫克/千克5-CT的小鼠表现出显著的辨别能力。这种长时间延迟的记忆增强效应是由5-HT7R激活有效介导的，因为它被10毫克/千克的SB-269970阻断，但未被10毫克/千克的WAY-100135或10毫克/千克的GR-127935阻断。
这些数据表明，5-HT7R对物体识别巩固过程中涉及的认知过程具有持续性调节作用。因此，5-HT7R可能是治疗与正常或病理性衰老相关的记忆功能障碍（尤其是情景相关缺陷）的一个有前景的靶点。
