The role of 5-HT1a and 5-HT2a receptors in attention and motor control: a mechanistic study in healthy volunteers.
BACKGROUND
Various studies have demonstrated a modulating role for serotonin in attention. Selective serotonin inhibitors have repeatedly been shown to impair performance in sustained attention tasks.


OBJECTIVE
To assess the contribution of serotonin reuptake inhibition and specific blockade of the pre-synaptic 5-HT(1a) receptor and the 5-HT(2a) receptor to deficits in attention.


METHODS
The study was conducted according to a randomized, double-blind, placebo controlled, four-way crossover design including 16 healthy volunteers. Treatments consisted of oral administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram 20 mg + placebo; escitalopram 20 mg + ketanserin (5-HT(2a) antagonist), 50 mg; escitalopram 20 mg + pindolol (5-HT(1a) antagonist) 10 mg; and placebo + placebo on four separate days. A range of performance tasks were conducted to assess the subjects' attention and motor functions.


RESULTS
Escitalopram administered alone impaired tracking performance in a divided attention task. The combination of escitalopram and pindolol and escitalopram and ketanserin impaired divided attention as compared to placebo. In addition, escitalopram and ketanserin impaired sustained attention. Divided attention impairment observed after combined treatments did not significantly differ from impairments after escitalopram alone. Sustained attention impairment observed after combined escitalopram and ketanserin significantly differed from escitalopram alone.


CONCLUSIONS
5HT(1a) blockade hardly affected SSRI effects on attention. Additional 5HT(2a) blockade, however, produced impairments of sustained attention and motor impulse control.
Wingen
Marleen
M
Faculty of Psychology, Department of Neurocognition (Experimental Psychopharmacology Unit), Brain and Behaviour Institute, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. m.wingen@psychology.unimaas.nl
Kuypers
Kim P C
KP
Ramaekers
Johannes G
JG
D000284:Administration, Oral; D000328:Adult; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010869:Pindolol / Q000008:administration & dosage / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects / Q000502:physiology
D015283:Citalopram; D007650:Ketanserin; D010869:Pindolol; D044282:Receptor, Serotonin, 5-HT1A; D044402:Receptor, Serotonin, 5-HT2A; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors