Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats:: implication of the frontal cortex
Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats:: implication of the frontal cortex
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DOI：
10.1007/s00213-007-0934-5
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Millan, Mark J.
中科院分区：
文献类型：
--
作者：
Loiseau, Florence;Dekeyne, Anne;Millan, Mark J.
原理：5 - HT6受体拮抗剂可改善啮齿动物的认知过程。然而，它们的作用位点尚未被探究，且它们对社会记忆的影响也鲜有研究。
目的：我们通过全身给药或局部给药至额叶皮质（FCX）、纹状体或基底核大细胞部（NBM），研究了5 - HT6受体配体对大鼠社会记忆的影响。
材料和方法：社会识别测试基于成年大鼠在两个5分钟测试阶段中的第二个阶段识别较年幼同类的能力。在无阶段间间隔的实验程序中，检测了药物单独作用以及逆转毒蕈碱拮抗剂东莨菪碱（1.25 mg/kg，皮下注射）诱导的“遗忘”的能力。在另一个因120分钟阶段间间隔而诱导出自然识别缺陷的实验程序中，也研究了药物潜在的促记忆效应。
结果：5 - HT6受体激动剂WAY - 181187（10.0 mg/kg，腹腔注射）显著损害社会识别能力。这种效应可被5 - HT6受体拮抗剂SB - 271046（20.0 mg/kg，腹腔注射）和SB - 258585（10.0 mg/kg，腹腔注射）消除。这些药物也消除了东莨菪碱诱导的遗忘（分别为10.0和2.5 mg/kg，腹腔注射），并逆转了延迟诱导的缺陷（分别为10.0 - 20.0和2.5 - 10.0 mg/kg，腹腔注射）。将WAY - 181187注入FCX显著损害社会识别能力（0.16 - 0.63μg/侧）。相反，将SB - 271046注入FCX（2.5 - 5.0μg/侧），但注入纹状体或NBM则无此效果，可显著逆转自然缺陷。
结论：这些结果表明5 - HT6受体通过在FCX中的作用调节社会识别，并且支持它们作为治疗认知功能受损的精神疾病的靶点的相关性。
Rationale 5-HT6 receptor antagonists improve cognitive processes in rodents. However, their site(s) of action remains unexplored and their influence upon social memory has been little investigated.Objectives We examined the influence of 5-HT6 receptor ligands upon social memory in rats by use of systemic or local administration into the frontal cortex (FCX), striatum, or nucleus basalis magnocellularis (NBM).Materials and methods The social recognition test is based upon the ability of an adult rat to recognize a younger conspecific during the second of two 5-min sessions. In a procedure without an inter-session interval, the actions of drugs alone and the ability to reverse "amnesia" induced by the muscarinic antagonist, scopolamine (1.25 mg/kg, s.c.), were examined. The potential promnesic effect of drugs was also investigated in another procedure where a spontaneous deficit of recognition was induced by a 120-min inter-session interval.Results The 5-HT6 receptor agonist, WAY-181187 (10.0 mg/kg, i.p.), significantly impaired social recognition. This effect was abolished by the 5-HT6 receptor antagonists, SB-271046 (20.0 mg/kg, i.p.) and SB-258585 (10.0 mg/kg, i.p.). These agents also abolished scopolamine-induced amnesia (10.0 and 2.5 mg/kg, i.p., respectively) and reversed the delay-induced deficit (10.0-20.0 and 2.5-10.0 mg/kg, i.p., respectively). WAY-181187 into the FCX significantly impaired social recognition (0.16-0.63 mu g/side). Conversely, SB-271046 into the FCX (2.5-5.0 mu g/side), but neither into the striatum nor the NBM, significantly reversed spontaneous deficit.Conclusion These results indicate that 5-HT6 receptors modulate social recognition by actions in the FCX and underpin their pertinence as targets for the treatment of psychiatric disorders in which cognitive function is compromised.