Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5

  title={Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5},
  author={R G Morris and E. Anderson and Gary Lynch and Michel Baudry},
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)1 and that exhibit a peculiar dependency on membrane voltage in becoming active only on depolarization2,3. 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… 

Distinct components of spatial learning revealed by prior training and NMDA receptor blockade

It is reported that the AP5-induced learning deficit can be almost completely prevented if rats are pretrained in a different watermaze before administration of the drug.

Spatial learning without NMDA receptor-dependent long-term potentiation

It is reported that NPC17742 completely blocked dentate gyrus LTP but did not prevent normal spatial learning in rats that had been made familiar with the general task requirements by non-spatial pretraining, indicating that this form of LTP is not required for normal spatiallearning in the watermaze.

Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine

It is reported here that intraventricular infusions of B6B21 significantly enhances acquisition rates in hippocampus-dependent trace eye blink conditioning in rabbits, halving the number of trials required to reach a criterion of 80% conditioned responses.

Differential effects of ibotenic acid lesions of the hippocampus and blockade of N-methyl-{d}-aspartate receptor-dependent long-term potentiation on contextual processing in rats.

Results indicate that rats are capable of processing contextual information in the absence of N-methyl-D-aspartate (NMDA) receptor-dependent LTP and demonstrate an important dissociation between the effects of hippocampal lesions and the blockade of NMDA receptors in the hippocampus.

Pharmacological evidence for a role of long-term potentiation in memory.

  • I. Izquierdo
  • Biology, Psychology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1994
The data reviewed here lend strong support to the hypothesis that LTP in areas of the brain known to be responsible for the storage and retrieval of declarative memories underlies memory processes.



Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones

Using voltage-clamp experiments on mouse spinal cord neurones, it is shown that the voltage-sensitivity of NMDA action is greatly reduced on the withdrawal of physiological concentrations (∼1 mM) of Mg2+ from the extracellular fluid, providing further evidence that Mg 2+ blocks inward current flow through ion channels linked to NMDA receptors.

Magnesium gates glutamate-activated channels in mouse central neurones

The voltage dependence of the NMDA receptor-linked conductance appears to be a consequence of the voltage dependenceof the Mg2+ block and its interpretation does not require the implication of an intramembrane voltage-dependent ‘gate’.

The antagonism of amino acid‐induced excitations of rat hippocampal CA1 neurones in vitro.

DGG and APV did not affect ACh excitations and these selective antagonists should be of value in studying the involvement of the excitatory amino acids in synaptic transmission in the hippocampus, while PDA, GDEE, D‐ and L‐APB may be less useful in this regard.

Place navigation impaired in rats with hippocampal lesions

It is reported that, in addition to a spatial discrimination impairment, total hippocampal lesions also cause a profound and lasting placenavigational impairment that can be dissociated from correlated motor, motivational and reinforcement aspects of the procedure.

Anticonvulsant action of excitatory amino acid antagonists.

Specific antagonists of excitation that is caused by amino acids provide a new class of anticonvulsant agents, and the most potent such compound was 2-amino-7-phosphonoheptanoic acid.

A comparison of the contributions of the frontal and parietal association cortex to spatial localization in rats.

The results suggest that the frontal andParietal cortex of rats play different roles in the control of spatial orientation but do not support the view that egocentric and allocentric spatial orientation are related to frontal and parietal mechanisms, respectively.

The biochemistry of memory: a new and specific hypothesis.

A synaptic process with properties required for an intermediate step in memory storage is uncovered and hypothesized to be responsible for those forms of memory localized in the telencephalon.