Effects of intrahippocampal injections of N-methyl-D-aspartate receptor antagonists and scopolamine on working and reference memory assessed in rats by a three-panel runway task.
In order to elucidate the roles of hippocampal N-methyl-D-aspartate-type excitatory amino acid receptors in working and reference memory in rats, the effects of intrahippocampal injections of selective and competitive N-methyl-D-aspartate receptor antagonists such as CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid), 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid and 2-amino-5-phosphonovaleric acid on this behavior were examined with a three-panel runway task. The results were compared with the effect of the muscarinic receptor antagonist scopolamine. In the working memory task, CGS 19755 and 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid at 10 and 32 ng/side, injected bilaterally into the dorsal hippocampus before testing, produced a significant increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). This also occurred after the rats were given systemic injection of these drugs at 3.2 and 10 mg/kg. In the reference memory task, neither CGS 19755 nor 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid affected the number of errors, whether given at doses up to 32 ng/side intrahippocampally or up to 10 mg/kg systemically. Working memory errors also increased significantly after intrahippocampal injections of d-2-amino-5-phosphonovaleric acid at 100 and 320 ng/side, but were not affected by I-2-amino-5-phosphonovaleric acid at doses up to 1 microgram/side. On the other hand, intrahippocampal scopolamine at 1.0 and 3.2 micrograms/side increased significantly working memory errors, without affecting reference memory errors.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
M
M
Ohno
T
T
Yamamoto
S
S
Watanabe
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010875:Pipecolic Acids / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology*
D010875:Pipecolic Acids; D010879:Piperazines; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; C053672:selfotel; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D012601:Scopolamine