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The Journal of Neuroscience, April 1, 1998, 18(7):2748-2763
Facilitative Effects of the Ampakine CX516 on Short-Term Memory
in Rats: Correlations with Hippocampal Neuronal Activity
Robert E.
Hampson1,
Gary
Rogers2,
Gary
Lynch3, and
Sam A.
Deadwyler1
1 Department of Physiology and Pharmacology, Wake
Forest University School of Medicine, Winston Salem, North Carolina
27157, 2 Cortex Pharmaceuticals, Irvine, California 92718, and 3 Department of Psychiatry, University of California,
Irvine, California 92715
In the companion article (), the ampakine CX516
(Cortex Pharmaceuticals) was shown to produce a marked facilitation of
performance of a spatial delayed-nonmatch-to-sample (DNMS) task in
rats. Injections of the drug before each daily session produced a
marked and progressive improvement in performance at longer delays (>5
sec) that persisted for 7 d after drug treatment was terminated.
In most animals (n = 9) the increase in performance carried over to the intervening vehicle for days, whereas in others (n = 3) the effects dissipated within the session
according to the pharmacological half-life of CX516. In this article we
report firing correlates of simultaneously recorded cells in the CA1 and CA3 fields of the hippocampus over the period in which DNMS performance was facilitated by CX516. Sample and Delay period firing
was enhanced by 100-350% under CX516 and increased progressively over
days as did DNMS performance. The firing increases were restricted to
correct trials only and were largest on trials with long delays. Firing
in the intertrial interval was also altered, but in a manner consistent
with a previously demonstrated reduction in between-trial proactive
interference by CX516. Finally, in animals in which the effects of
CX516 were restricted to when the drug was actually present (i.e., no
carryover effects), increased cell firing also paralleled the time
course of the performance increase. Results are discussed with respect
to the actions of ampakines on hippocampal cellular and synaptic
processes that underlie DNMS performance.
Key words:
ampakine; hippocampus; learning; memory; neuron
ensembles; AMPA receptors
Copyright © 1998 Society for Neuroscience 0270-6474/98/1872748-16$05.00/0
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