Systemic NMDA antagonist CGP-37849 produces non-specific impairment in a working memory task: the effect does not resemble those of AP5 and of lesions of the hippocampus or fornix.
The N-methyl-D-aspartate (NMDA) receptor antagonist CGP-37849 (D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid), administered i.p. (2.0 and 4.0 mg/kg), impaired rats' performance in a delayed matching-to-sample working memory task. This task is sensitive to hippocampal/fornix lesions or intracerebroventricular (i.c.v.) administration of another NMDA antagonist, AP5 (2-amino-5-phosphono-pentanoic acid) in a stimulus-specific manner: the highest impairment when simple stimuli are used repeatedly; moderate impairment when complex stimuli are used repeatedly; and no impairment when complex stimuli are used in a pseudo-trial-unique fashion. The effect of CGP-37849, unlike those of surgical lesions and of AP5, was not stimulus-specific and therefore cannot be solely attributed to blockade of NMDA-dependent long-term potentiation (LTP) in the hippocampus. We infer that systemic administration of NMDA antagonists may affect a broad range of anatomical structures thereby interfering with other neural mechanisms of memory and motor performance.
Gutnikov
S A
SA
Department of Experimental Psychology, Oxford University, U.K. sg@vax.ox.ac.uk
Rawlins
J N
JN
D015763:2-Amino-5-phosphonovalerate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D017774:Long-Term Potentiation; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D008570:Memory, Short-Term / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D051381:Rats
C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate