Effects of the 5-HT2A agonist psilocybin on mismatch negativity generation and AX-continuous performance task: Implications for the neuropharmacology of cognitive deficitsin schizophrenia

Abstract

Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation ofthe auditory event-related potential(ERP)mismatch negativity(MMN) and the performance of an ‘AX'-type continuous performance test (AX-CPT)-measures of auditory and visualcontext-dependent information processing-in a similar manner as observed in schizophrenia.This placebo-controlled study investigated effects of the 5-HT2A receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin administration induced significant performance deficits in the AX-CPT, but failed to reduce MMN generationsignificantly. These results indirectly support evidence that deficient MMN generation in schizophrenia may be a relatively distinctmanifestation of deficient NMDAR functioning. In contrast, secondary pharmacologicaleffects shared by NMDAR antagonists and the5-HT2A agonist (ie disruption of glutamatergic neurotransmission) may be the mechanism underlying impairments in AX-CPTperformance observed during both psilocybin and ketamine administration. Comparable deficits in schizophrenia may result fromindependent dysfunctions of 5-HT2A and NMDAR-related neurotransmission. © 2003 American College of Neuropsychopharmacology.