NMDA receptor antagonists antagonize the facilitatory effects of post-training intra-basolateral amygdala NMDA and physostigmine on passive avoidance learning.
In the present study, the effects of post-training intra-basolateral amygdala (BLA) injection of an N-methyl-d-aspartate (NMDA) receptor agonist and competitive or noncompetitive antagonists, on memory retention of passive avoidance learning was measured in the presence and absence of physostigmine in rats. Intra-BLA administration of lower doses of NMDA (10(-5) and 10(-4) microg/rat) did not affect memory retention, although higher doses of the drug (10(-3), 10(-2) and 10(-1) microg/rat) increased memory retention. The greatest response was obtained with 10(-1) microg/rat of the drug. The different doses of the competitive NMDA receptor antagonist DL-AP5 (1, 3.2 and 10 microg/rat) and noncompetitive NMDA receptor antagonist MK-801 (0.5, 1 and 2 microg/rat) decreased memory retention in rats dose dependently. Both competitive and noncompetitive NMDA receptor antagonists reduced the effect of NMDA (10(-2) microg/rat). In another series of experiments, intra-BLA injection of physostigmine (2, 3 and 4 microg/rat) improved memory retention. Post-training co-administration of lower doses of NMDA (10(-5) and 10(-4) microg/rat) and physostigmine (1 microg/rat), doses which were ineffective when given alone, significantly improved the retention latency. The competitive and noncompetitive NMDA receptor antagonists, DL-AP5 and MK-801, decreased the effect of physostigmine (2 microg/rat). Atropine decreased memory retention by itself and potentiated the response to DL-AP5 and MK-801. It may be concluded that amygdalar NMDA receptor mechanisms interact with cholinergic systems in the modulation of memory.
Jafari-Sabet
Majid
M
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. jafarisa@sina.tums.ac.ir
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D010830:Physostigmine