Impairment of specific episodic memory processes by sub-psychotic doses of ketamine: the effects of levels of processing at encoding and of the subsequent retrieval task.
BACKGROUND
The precise nature of the impact of the N-methyl-D-aspartate antagonist, ketamine, upon human episodic memory, has yet to be elucidated fully.


OBJECTIVE
This study sought to assess the effects of ketamine on the sub-processes facilitating memory encoding and retrieval.


METHODS
We evaluated the effects of the drug on a series of memory performance measures depending upon whether it was administered at the encoding or retrieval stage and on the nature of the encoding task used. Twelve healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. Intravenous infusions of placebo, 50 ng/ml ketamine or 100 ng/ml ketamine were administered. We investigated the effects of ketamine on three key aspects of episodic memory: encoding vs retrieval processes, source memory, and depth of processing. Data were analysed using both multinomial modelling and standard measures of item discrimination and response bias.


RESULTS
Deleterious effects of ketamine on episodic memory were primarily attributable to its effects on encoding, rather than retrieval processes. Recognition memory was impaired for items encoded at an intermediate level of processing, but preserved for shallowly and deeply encoded items. Increased source guessing bias was also observed when encoding took place under ketamine.


CONCLUSIONS
The effects of ketamine upon episodic memory seem, therefore, to predominate at encoding. Furthermore, our results are also consistent with a specific impairment of encoding processes that result in subsequent recollective, as opposed to familiarity-based, retrieval. The observed effects are compatible with memory deficits seen in schizophrenia and thus provide some support for the ketamine model of the disease.
Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, P.O. Box 255, Hills Road, Cambridge, CB2 2QQ, UK.
Garry D
GD
Honey
Rebekah A E
RA
Honey
Sam R
SR
Sharar
Danielle C
DC
Turner
Edith
E
Pomarol-Clotet
Dharshan
D
Kumaran
Jon S
JS
Simons
Xiangen
X
Hu
Michael D
MD
Rugg
Edward T
ET
Bullmore
Paul C
PC
Fletcher
D000293:Adolescent; D000328:Adult; D001143:Arousal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008875:Middle Aged; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D012153:Retention, Psychology / Q000187:drug effects; D014706:Verbal Learning / Q000187:drug effects*
D016202:N-Methylaspartate; D007649:Ketamine