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 in operant delayed matching/or nonmatching to position (DMTP/DNMTP) tasks, as both delay-dependent and -independent disruption of choice accuracy has been found following N-methyl-D-aspartate (NMDA) receptor blockade. Using a within-subjects experimental design, the effect of the competitive NMDA receptor 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 the DNMTP task (0-16-s delay in intervals). Metal barriers were inserted between the food magazine and levers to inhibit the use of mediating strategies, such as orientation towards the correct lever during the delay interval, because this behavior may contribute to the delay-dependent disruption noted in previous studies. It was found that EAA 494 did not modify working memory either in the presence or absence of barriers. However, a dose-dependent impairment of task performance was recorded, notably in the presence of barriers. These results indicate that competitive blockade of NMDA receptors with EAA 494 does not result in impaired working memory in rats and parallel the lack of effect of the compound upon working memory in humans. Activation of NMDA receptors does not appear to be essential for the performance of spatial tasks requiring working memory.
Ballard
T M
TM
Novartis Pharma Inc., Nervous Systems Department, WSJ-386.226, CH-4002, Basel, Switzerland.
Mcallister
K H
KH
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012201:Reward; D012601:Scopolamine / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494; D012601:Scopolamine