Effects of agonists and antagonists of some serotonin-receptor subtypes on memory and their modulation by the 5-HT-uptake inhibitor fluoxetine.

V D Petkov, R Kehayov
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Abstract

The memory effects of agonists and antagonists of some serotonin (5-HT)-receptor subtypes were studied in experiments on rats using the method for passive avoidance with punishment reinforcement (step-down). The 5-HT1A-receptor agonist buspirone (1 mg/kg i.p.) elicited behavioural responses which suggested the lack of pronounced effect on learning and retention; the 5-HT1A-receptor antagonists NAN-190 (1 mg/kg i.p.) and pindolol (6 mg/kg i.p.) impaired retention tested 24 hours and 7 days after training as compared to controls. The 5-HT2-receptor antagonist ritanserin (1 mg/kg i.p.) impaired retention tested 24 hours and 7 days after training as compared to controls, while the 5-HT3-receptor antagonist ondansetron (0.1 mg/kg i.p.) improved it. The 5-HT1/5-HT2-receptor antagonist dotarizine (50 mg/kg orally), characterized by a calcium-antagonistic action, too, exerted some facilitating effect on learning. Most of the effects of the 5-HT-receptor agonists and antagonists were changed when the 5-HT concentration in the synaptic region was increased by the 5-HT-uptake inhibitor fluoxetine (20 mg/kg orally). The results suggest different participation of 5-HT1A-, 5-HT2- and 5-HT3-receptors in the mechanisms of memory process and its modulation by the serotonin level in the cerebral serotonergic synapses.

某些5-羟色胺受体亚型激动剂和拮抗剂对记忆的影响及其被5-羟色胺摄取抑制剂氟西汀调节。
在大鼠实验中,采用被动回避加惩罚强化(降压)的方法研究了5-羟色胺受体激动剂和拮抗剂的记忆效应。5- ht1a受体激动剂丁螺环酮(1 mg/kg i.p)引起的行为反应表明对学习和记忆没有明显的影响;与对照组相比,5- ht1a受体拮抗剂NAN-190 (1mg /kg i.p)和品多洛尔(6mg /kg i.p)在训练后24小时和7天测试了潴留受损。与对照组相比,5- ht2受体拮抗剂利坦色林(1 mg/kg i.p)在训练后24小时和7天测试中损害了潴留,而5- ht3受体拮抗剂昂丹西琼(0.1 mg/kg i.p)改善了潴留。5- ht1 /5- ht2受体拮抗剂多他嗪(50 mg/kg口服)也具有钙拮抗作用,对学习也有一定的促进作用。当5-HT摄取抑制剂氟西汀(20mg /kg口服)增加突触区5-HT浓度时,5-HT受体激动剂和拮抗剂的大部分作用发生改变。结果提示5-HT1A-、5-HT2-和5- ht3受体参与记忆过程的不同机制及其受脑5-羟色胺能突触中5-羟色胺水平的调节。
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