The NMDA antagonist EAA 494 does not impair working memory in an operant DNMTP task in rats

There is contrasting evidence for an impairment of spatial working memory i n operant delayed matching/or nonmatching to position (DMTP/DNMTP) tasks, a s both delay-dependent and -independent disruption of choice accuracy has b een found following N-methyl-D-aspartate (NMDA) receptor blockade. Using a within-subjects experimental design, the effect of the competitive NMDA rec eptor antagonist, EAA 494 (D-CPP-ene) (1, 1.5, 2 mg/kg IP 30 min prior), on working memory was investigated in male Lister Hooded rats pretrained to t he DNMTP task (0-16-s delay in intervals). Metal barriers were inserted bet ween the food magazine and levers to inhibit the use of mediating strategie s, such as orientation towards the correct lever during the delay interval, because this behavior may contribute to the delay-dependent disruption not ed in previous studies. It was found that EAA 494 did not modify working me mory either in the presence or absence of barriers. However, a dose-depende nt impairment of task performance was recorded, notably in the presence of barriers. These results indicate that competitive blockade of NMDA receptor s with EAA 494 does not result in impaired working memory in rats and paral lel the lack of effect of the compound upon working memory in humans. Activ ation of NMDA receptors does not appear to be essential for the performance of spatial tasks requiring working memory. (C) 2000 Elsevier Science.