Orienting of attention in the 5HT2A agonist and NMDA antagonist model of psychosis

Patients with schizophrenia exhibit disturbances of orienting of attention. However, findings have been inconsistent. Hallucinogen challenges have been used as models for psychosis. The NMDA antagonist state resembles undifferentiated psychoses, whereas the 5-HT2A agonist state is considered as a model for psychoses with prominent positive symptoms. The aim of this study was to investigate orienting of attention in the human NMDA antagonist (S-ketamine) and 5-HT2A agonist (DMT) models of psychosis. Fifteen healthy volunteers participated in a randomized, double-blind, cross-over study with two doses of DMT and S-ketamine. Nine subjects completed both experimental days. Overall, both hallucinogens slowed down RTs dose-dependently (DMT > S-ketamine) and DMT diminished the general response facilitating (alerting) effect of cues. Inhibition of Return (IOR), i.e. 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 protects 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 different psychotic manifestations, but particularly those with prominent positive symptoms.