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Selective verbal and spatial memory impairment after 5-HT_1A and 5-HT_2A receptor blockade in healthy volunteers pre-treated with an SSRI

Experimental Psychopharmacology Unit, Faculty of Psychology, Brain & Behaviour Institute, Maastricht University, the Netherlands, m.wingen{at}psychology.unimaas.nl

K.P.C. Kuypers

Experimental Psychopharmacology Unit, Faculty of Psychology, Brain & Behaviour Institute, Maastricht University, the Netherlands

J.G. Ramaekers

Experimental Psychopharmacology Unit, Faculty of Psychology, Brain & Behaviour Institute, Maastricht University, the Netherlands.

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.

Key Words: memory • serotonin • escitalopram • pindolol • ketanserin

This version was published on July 1, 2007

Journal of Psychopharmacology, Vol. 21, No. 5, 477-485 (2007)
DOI: 10.1177/0269881106072506


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