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Effects of the 5-HT(2A) Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Perfo

Effects of the 5-HT(2A) Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Perfo

  1. Phungushead
    Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an \'AX\'-type continuous performance test (AX-CPT)-measures of auditory and visual context-dependent information processing-in a similar manner as observed in schizophrenia. This placebo-controlled study investigated effects of the 5-HT(2A) 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 generation significantly. These results indirectly support evidence that deficient MMN generation in schizophrenia may be a relatively distinct manifestation of deficient NMDAR functioning. In contrast, secondary pharmacological effects shared by NMDAR antagonists and the 5-HT(2A) agonist (ie disruption of glutamatergic neurotransmission) may be the mechanism underlying impairments in AX-CPT performance observed during both psilocybin and ketamine administration. Comparable deficits in schizophrenia may result from independent dysfunctions of 5-HT(2A) and NMDAR-related neurotransmission.Neuropsychopharmacology (2003) 28, 170-181. doi:10.1038/sj.npp.1300005