Selective verbal and spatial memory impairment after 5-HT1A and 5-HT2A receptor blockade in healthy volunteers pre-treated with an SSRI.

Full Abstract

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.

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Author information

Author/s: Wingen, M (M); Kuypers, K P C (KP); Ramaekers, J G (JG);

Affiliation: Experimental Psychopharmacology Unit, Faculty of Psychology, Brain & Behaviour Institute, Maastricht University, The Netherlands. m.wingen(-atsign-)psychology.unimaas.nl

Journal and publication information

Publication Type: Journal Article; Randomized Controlled Trial

Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol), published in United States. (Language: eng)

Reference: 2007-Jul; vol 21 (issue 5) : pp 477-85

Dates: Created 2007/07/31; Completed 2007/10/04;

PMID: 17092965, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Administration, Oral
Adult
Affect - drug effects
Brain - drug effects; metabolism
Citalopram - pharmacology
Cognition - drug effects
Cross-Over Studies
Double-Blind Method
Female
Humans
Ketanserin - administration & dosage; pharmacology

Male
Mental Recall - drug effects
Pindolol - administration & dosage; pharmacology
Receptor, Serotonin, 5-HT1A - antagonists & inhibitors; metabolism
Receptor, Serotonin, 5-HT2A - antagonists & inhibitors; metabolism
Reference Values
Serotonin - metabolism
Serotonin Antagonists - administration & dosage; pharmacology
Serotonin Uptake Inhibitors - pharmacology
Space Perception - drug effects
Verbal Learning - drug effects

Associated Chemicals: Receptor, Serotonin, 5-HT2A (0) ; Serotonin Antagonists (0) ; Serotonin Uptake Inhibitors (0) ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; Pindolol (13523-86-9) ; Serotonin (50-67-9) ; Citalopram (59729-33-8) ; Ketanserin (74050-98-9)

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