Walker Ellen A, Foley John J
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140, USA.
Behav Pharmacol. 2010 Mar;21(2):83-9. doi: 10.1097/FBP.0b013e328337bde7.
Although the neurotransmitter, 5-hydroxytryptamine (serotonin, 5-HT), has been implicated as a mediator of learning and memory, the specific role of 5-HT receptors in rodents requires further delineation. In this study, 5-HT2C receptor ligands of varying relative intrinsic efficacies were tested in a mouse learning and memory model called autoshaping-operant. On day 1, mice were placed in experimental chambers and presented with a tone on a variable interval schedule. The tone remained on for 6 s or until a nose-poke response occurred to produce a dipper with Ensure solution. Mice were then injected with saline, MK212 (full agonist), m-chlorophenylpiperazine (partial agonist), mianserin, and SB206 553 (inverse agonists), and methysergide and (+)-2-bromo lysergic acid diethylamide (+)-hydrogen tartrate (neutral antagonists). Each compound was injected after either 1 or 2-h acquisition sessions on day 1 to investigate the role of acquisition session length on consolidation. Day 1 injection of the 5-HT2C inverse agonist mianserin produced greater retrieval impairments of the autoshaped operant response on day 2 than any other agent tested. Furthermore, decreasing the length of the acquisition session to 1h significantly increased the difficulty of the autoshaping task further modulating the consolidation effects produced by the 5-HT2C ligands tested.
尽管神经递质5-羟色胺（血清素，5-HT）被认为是学习和记忆的介质，但5-HT受体在啮齿动物中的具体作用仍需进一步明确。在本研究中，在一种名为自动成型操作的小鼠学习和记忆模型中测试了具有不同相对内在效能的5-HT2C受体配体。在第1天，将小鼠放入实验箱中，并以可变间隔时间表呈现一个音调。音调持续6秒或直到出现鼻戳反应以产生装有安素溶液的勺子。然后给小鼠注射生理盐水、MK212（完全激动剂）、间氯苯哌嗪（部分激动剂）、米安色林和SB206553（反向激动剂），以及麦角新碱和（+）-2-溴麦角酸二乙酰胺（+）-酒石酸氢盐（中性拮抗剂）。在第1天的1小时或2小时习得训练后注射每种化合物，以研究习得训练时长对巩固的作用。第1天注射5-HT2C反向激动剂米安色林在第2天对自动成型操作反应产生的检索损伤比测试的任何其他药物都更大。此外，将习得训练的时长减少到1小时会显著增加自动成型任务的难度，进一步调节所测试的5-HT2C配体产生的巩固效果。
