Differences in the effects of zolpidem and diazepam on recurrent inhibition and long-term potentiation in rat hippocampal slices

Abstract

We used the CA1 region of rat hippocampal slices to compare the effects of non-benzodiazepine zolpidem, which binds preferentially to the omega1 sites of gamma-aminobutyric acid A (GABA(A)) receptors, and of benzodiazepine diazepam, which binds equipotently to the omega1 and omega2 sites, on the hippocampal inhibitory mechanism and on long-term potentiation (LTP), a possible cellular mechanism for memory. First, 1 microM diazepam had an enhancing effect on recurrent inhibition by alveus stimulation of orthodromically-induced population spikes, but 1 microM zolpidem had no significant effect. Second, 1 microM diazepam blocked LTP induction of the population spikes, whereas 1 microM zolpidem had no such effect. Only at a higher concentration of 10 microM, zolpidem had a significant effect on recurrent inhibition and LTP. These findings suggest that only the omega2 sites are mainly involved in modulation of the hippocampal inhibitory mechanism and LTP, and that the low affinity of zolpidem for the omega2 sites may account for less memory impairment caused by zolpidem than by benzodiazepines.