Facilitative Effects of the Ampakine CX516 on Short-Term Memory in Rats: Correlations with Hippocampal Neuronal Activity

In the companion article (Hampson et al., 1998), 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.

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