Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Morris, R., Anderson, E, Lynch, G., & Baudry, M Nature, 319(6056):774-6, 1986.
abstract   bibtex   
Recent work has shown that the hippocampus contains a class of receptors for the excitatory amino acid glutamate that are activated by N-methyl-D-aspartate (NMDA) and that exhibit a peculiar dependency on membrane voltage in becoming active only on depolarization. Blockade of these sites with the drug aminophosphonovaleric acid (AP5) does not detectably affect synaptic transmission in the hippocampus, but prevents the induction of hippocampal long-term potentiation (LTP) following brief high-frequency stimulation. We now report that chronic intraventricular infusion of D,L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage, without affecting visual discrimination learning, which is not. The L-isomer of AP5 did not produce behavioural effects. AP5 treatment also suppressed LTP in vivo. These results suggest that NMDA receptors are involved in spatial learning, and add support to the hypothesis that LTP is involved in some, but not all, forms of learning.
@Article{Morris1986,
  author   = {RG Morris and E Anderson and GS Lynch and M Baudry},
  journal  = {Nature},
  title    = {Selective impairment of learning and blockade of long-term potentiation by an {N}-methyl-{D}-aspartate receptor antagonist, {AP}5.},
  year     = {1986},
  number   = {6056},
  pages    = {774-6},
  volume   = {319},
  abstract = {Recent work has shown that the hippocampus contains a class of receptors
	for the excitatory amino acid glutamate that are activated by N-methyl-D-aspartate
	(NMDA) and that exhibit a peculiar dependency on membrane voltage
	in becoming active only on depolarization. Blockade of these sites
	with the drug aminophosphonovaleric acid (AP5) does not detectably
	affect synaptic transmission in the hippocampus, but prevents the
	induction of hippocampal long-term potentiation (LTP) following brief
	high-frequency stimulation. We now report that chronic intraventricular
	infusion of D,L-AP5 causes a selective impairment of place learning,
	which is highly sensitive to hippocampal damage, without affecting
	visual discrimination learning, which is not. The L-isomer of AP5
	did not produce behavioural effects. AP5 treatment also suppressed
	LTP in vivo. These results suggest that NMDA receptors are involved
	in spatial learning, and add support to the hypothesis that LTP is
	involved in some, but not all, forms of learning.},
  keywords = {Amygdala, Animals, Evaluation Studies, Hippocampus, Human, Learning, Long-Term Potentiation, Memory, Models, Neurological, Neural Pathways, Neuronal Plasticity, Support, Non-U.S. Gov't, Synapses, 2-Amino-5-phosphonovalerate, Electric Stimulation, Isomerism, Rats, Receptors, N-Methyl-D-Aspartate, Neurotransmitter, Valine, Visual Perception, 2869411},
}

Downloads: 0