Wingen M, Kuypers K P C, Ramaekers J G
Experimental Psychopharmacology Unit, Faculty of Psychology, Brain & Behaviour Institute, Maastricht University, The Netherlands.
J Psychopharmacol. 2007 Jul;21(5):477-85. doi: 10.1177/0269881106072506. Epub 2006 Nov 8.
Serotonergic neurotransmission has been implicated in memory impairment. It is unclear however if memory performance is mediated through general 5-HT availability, through specific 5-HT receptors or both. The aim of the present study was to assess the contribution of 5-HT reuptake inhibition and specific blockade of 5-HT(1A) and 5-HT(2A) receptors to memory impairment. The study was conducted according to a randomized, double-blind, placebo-controlled, four-way cross-over design including 16 healthy volunteers. The treatment consisted of oral administration of escitalopram 20 mg + placebo, escitalopram 20 mg + ketanserin 50 mg, escitalopram 20 mg + pindolol 10 mg and placebo on 4 separate days with a washout period of minimum 7 days. Different memory tasks were performed including verbal memory, spatial working memory and reversal learning. Escitalopram showed an impairing effect on immediate verbal recall which nearly reached statistical significance. No effects of escitalopram were found on other types of memory. In combination with pindolol, immediate verbal recall was significantly impaired. Escitalopram in combination with ketanserin impaired spatial working memory significantly. No effects were found on reversal learning. Selective impairment of immediate verbal recall after a 5-HT(1A) partial agonist and selective impairment of spatial working memory performance after 5-HT(2A) receptor antagonist, both in combination with a selective serotonergic reuptake inhibitor (escitalopram), suggests that 5-HT(1A) and 5-HT(2A) receptors are distinctly involved in verbal and spatial memory.
血清素能神经传递与记忆障碍有关。然而，目前尚不清楚记忆表现是通过一般的5-羟色胺可用性、特定的5-羟色胺受体还是两者共同介导的。本研究的目的是评估5-羟色胺再摄取抑制以及5-羟色胺（1A）和5-羟色胺（2A）受体的特异性阻断对记忆障碍的影响。该研究按照随机、双盲、安慰剂对照、四交叉设计进行，纳入了16名健康志愿者。治疗包括在4个不同的日子分别口服20毫克艾司西酞普兰+安慰剂、20毫克艾司西酞普兰+50毫克酮色林、20毫克艾司西酞普兰+10毫克吲哚洛尔以及安慰剂，洗脱期至少为7天。进行了不同的记忆任务，包括言语记忆、空间工作记忆和逆向学习。艾司西酞普兰对即时言语回忆显示出损害作用，几乎达到统计学显著性。未发现艾司西酞普兰对其他类型的记忆有影响。与吲哚洛尔联合使用时，即时言语回忆显著受损。艾司西酞普兰与酮色林联合使用显著损害空间工作记忆。未发现对逆向学习有影响。5-羟色胺（1A）部分激动剂后即时言语回忆的选择性损害以及5-羟色胺（2A）受体拮抗剂后空间工作记忆表现的选择性损害，两者均与选择性血清素能再摄取抑制剂（艾司西酞普兰）联合使用，表明5-羟色胺（1A）和5-羟色胺（2A）受体分别参与言语和空间记忆。
