title: Inhibition of return in the human 5HT2A agonist and NMDA antagonist model of psychosis.
abstract: Patients with schizophrenia exhibit disturbances of orienting of attention. However, findings have been inconsistent. Pharmacologic challenges with hallucinogens have been used as models for psychosis. The NMDA antagonist state (PCP, ketamine) resembles undifferentiated psychoses with positive and negative symptoms, while the 5-HT(2A) agonist state (LSD, dimethyltryptamine (DMT)) is thought to be an appropriate model for psychoses with prominent positive symptoms. The aim of this study was to investigate orienting of attention in the human NMDA antagonist and 5-HT(2A) agonist models of psychosis. A total of 15 healthy volunteers participated in a randomized, double-blind, crossover study with a low and a high dose of DMT and S-ketamine, which elicited subtle 'prepsychotic' or full-blown psychotic symptoms (low and high dose, respectively). Nine subjects completed both experimental days with the two doses of both drugs. Overall, both hallucinogens slowed down reaction times dose dependently (DMT >S-ketamine) and DMT diminished the general response facilitating (alerting) effect of spatially neutral cues. Inhibition of Return (IOR), that is, the normal reaction time disadvantage for validly cued trials with exogenous cues and long cue target intervals, was blunted after both doses of DMT and the low dose of S-ketamine. IOR reflects an automatic, inhibitory mechanism of attention, which is thought to protect the organism from redundant, distracting sensory information. In conclusion, our data suggest a deficit of IOR in both hallucinogen models of psychosis, with the effect being clearer in the serotonin model. Blunted IOR may underlie or predispose to different psychotic manifestations, but particularly to those with prominent positive symptoms.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Cologne, Germany. e.gouzoulis@uni-koeln.de
authors.forename: Euphrosyne
authors.initials: E
authors.lastname: Gouzoulis-Mayfrank
authors.forename: Karsten
authors.initials: K
authors.lastname: Heekeren
authors.forename: Anna
authors.initials: A
authors.lastname: Neukirch
authors.forename: Martina
authors.initials: M
authors.lastname: Stoll
authors.forename: Carsten
authors.initials: C
authors.lastname: Stock
authors.forename: Joerg
authors.initials: J
authors.lastname: Daumann
authors.forename: Maja
authors.initials: M
authors.lastname: Obradovic
authors.forename: Karl-Artur
authors.initials: KA
authors.lastname: Kovar
mesh_terms: D000328:Adult; D001288:Attention / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D004130:N,N-Dimethyltryptamine / Q000633:toxicity*; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D011594:Psychometrics; D011605:Psychoses, Substance-Induced / Q000209:etiology* / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D058826:Serotonin 5-HT2 Receptor Agonists
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D058826:Serotonin 5-HT2 Receptor Agonists; D007649:Ketamine; D004130:N,N-Dimethyltryptamine