Source Paper
Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D- aspartate receptor antagonist AP5
Journal of Neuroscience • 1989
View Abstract
This paper reports a series of 5 experiments concerned with a possible role for N-methyl-D-aspartate (NMDA) receptors in certain types of learning. The results show that chronic intraventricular infusion of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (D,L- AP5) caused an impairment of spatial but not of visual discrimination learning in rats. Such selectivity of the learning impairment occurred despite widespread distribution of the drug throughout the CNS. AP5 sometimes caused a disturbance of sensorimotor function during learning, but one experiment addressing whether this disturbance could be responsible for the spatial learning impairment established that it was statistically independent. Another experiment showed that AP5 did not affect the retention of previously acquired spatial information. These behavioral effects were all obtained with a concentration of AP5 that, in a final study, was found to be sufficient to block hippocampal long-term potentiation (LTP) in vivo without affecting normal synaptic transmission. Taken together, these observations (1) implicate NMDA receptors in certain types of learning, and (2) extend recent work showing that saturation of LTP causes an anterograde spatial amnesia (McNaughton et al., 1986). A preliminary report of parts of this work has been published (Morris et al., 1986a).
Spatial Memory Retention Test
Objective: Assessment of retention of previously acquired spatial information following AP5 treatment
Gather these items before starting the experiment. Check off items as you prepare.
Materials1
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Protocol Steps
Spatial Information Acquisition
Rats acquire spatial information prior to AP5 treatment
Note: This is the learning phase before drug administration
View evidence from paper
“retention of previously acquired spatial information”
AP5 Administration
Chronic intraventricular infusion of AP5 is administered to rats
Note: Drug concentration was sufficient to block hippocampal LTP in vivo
View evidence from paper
“chronic intraventricular infusion of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (D,L-AP5)”
Retention Testing
Assessment of retention of previously acquired spatial information following AP5 treatment
Note: Results showed AP5 did not affect retention of previously acquired spatial information
View evidence from paper
“AP5 did not affect the retention of previously acquired spatial information”