Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors.
Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 microg/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.
Carter
Olivia L
OL
University of Queensland, Australia. ocarter@wjh.harvard.edu
Burr
David C
DC
Pettigrew
John D
JD
Wallis
Guy M
GM
Hasler
Felix
F
Vollenweider
Franz X
FX
D000328:Adult; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D011562:Psilocybin / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013028:Space Perception / Q000187:drug effects
D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D011562:Psilocybin; D007650:Ketanserin