title: Acute and chronic effects of ketamine on semantic priming: modeling schizophrenia?
abstract: Acute administration of the N-methyl-D-aspartate receptor antagonist ketamine induces schizophrenia-like symptoms in healthy volunteers; furthermore, a window on ketamine's chronic effects is provided by regular recreational users. The current study utilized both acute ketamine administration in healthy volunteers and chronic ketamine abusers to investigate semantic processing, one of the key cognitive deficits in schizophrenia. Semantic processing was examined using a semantic priming paradigm. In experiment 1, acute effects of low (75 ng/mL) and high (150 ng/mL) ketamine doses were compared in a placebo-controlled double-blind independent group design with 48 participants. In experiment 2, 19 regular recreational ketamine users were compared with 19 ketamine-naive polydrug controls and 26 non-drug-using controls. In both experiments, semantic priming parameters were manipulated to distinguish between ketamine's effects on (1) automatic and strategic processing and (2) the facilitation and inhibition components of semantic priming for strongly (directly) related primes and targets. Acute effects of ketamine on semantic priming for weakly (indirectly) related primes and targets were also assessed in experiment 1. Acutely, ketamine impaired the employment of strategic mechanisms but not automatic processing within both the direct and indirect semantic priming tasks. Acute ketamine administration also induced clear schizophrenia-like symptoms. Schizotypy traits in the cognitive and perceptual domains tended to correlate with increased semantic priming in long-term ketamine users. In summary, acute and chronic ketamine-induced changes partially mirrored the findings on semantic priming in schizophrenia.
authors.affiliation: Clinical Psychopharmacology Unit, University College London, London, United Kingdom. ana.stefanovic@ucl.ac.uk
authors.forename: Ana
authors.initials: A
authors.lastname: Stefanovic
authors.forename: Brigitta
authors.initials: B
authors.lastname: Brandner
authors.forename: Elissa
authors.initials: E
authors.lastname: Klaassen
authors.forename: Roman
authors.initials: R
authors.lastname: Cregg
authors.forename: Mayavaty
authors.initials: M
authors.lastname: Nagaratnam
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Bromley
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Das
authors.forename: Susan L
authors.initials: SL
authors.lastname: Rossell
authors.forename: Celia J A
authors.initials: CJ
authors.lastname: Morgan
authors.forename: H Valerie
authors.initials: HV
authors.lastname: Curran
mesh_terms: D000293:Adolescent; D000328:Adult; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D012565:Schizophrenic Psychology; D012660:Semantics; D019966:Substance-Related Disorders; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine