NMDA receptor modulation by D-cycloserine promotes episodic-like memory in mice

• Published in: Psychopharmacologia Vol. 193; no. 4; pp. 503 - 509
• Main Authors: ZLOMUZICA, Armin, DE SOUZA SILVA, Maria A, HUSTON, Joseph P, DERE, Ekrem
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-09-2007; Springer Nature B.V
• Subjects: Adult and adolescent clinical studies; Alzheimer's disease; Analysis of Variance; Animals; Antagonist drugs; Behavior, Animal; Biological and medical sciences; Biology; Clinical trials; Cycloserine; Cycloserine - administration & dosage; Cycloserine - pharmacology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists - pharmacology; Form Perception - drug effects; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Injections, Intraperitoneal; Learning; Male; Medical sciences; Memory; Memory - drug effects; Mice; Mice, Inbred C57BL; N-Methyl-D-aspartic acid receptors; Neurology; Organic mental disorders. Neuropsychology; Pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Random Allocation; Receptors, N-Methyl-D-Aspartate - agonists; Recognition, Psychology; Rodents; Space Perception - drug effects; Synaptic plasticity; Temporal variations; Time Perception - drug effects; Nervous system diseases; Alzheimer disease; Rodentia; Temporal order memory; Cognition; Glutamate receptor; Cycloserine; Cerebral disorder; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Object-place memory; Degenerative disease; NMDA receptor; Episodic memory; Alzheimer's disease
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-007-0816-x

NMDA-R (N-methyl-D-aspartate receptors) have been implicated in synaptic plasticity underlying one-trial learning of event-place associations. In rodents, episodic-like memory (ELM) of personally experienced events can be inferred from behavior that reflects the remembrance of the content (what kind of object was presented), place (where was this object placed), and temporal context (when was the object presented). We have previously shown that that D-cycloserine (DCS), an NMDA-R agonist, ameliorates stress-induced deficits in ELM.
In this study, we used an experimental protocol designed to detect promnestic drug effects and investigated whether DCS, which is known to enhance learning and memory, can induce ELM under conditions where mice normally do not show ELM.
Mice that have been treated i.p. with DCS (20 mg/kg) both remembered the temporal order in which two different objects had been encountered during two consecutive sample trials, as well as their spatial position during the sample trials. Most importantly, the test trial performance of these mice is compatible with ELM in terms of an integrated memory for unique experiences comprising "what", "where", and "when" information. In contrast, mice that have received either a saline injection or lower doses of DCS (0.2 and 2.0 mg/kg) did not show such an integrated ELM.
To our knowledge, this is the first report showing that DCS can promote ELM in mice.