DIFFERENCES IN THE EFFECTS OF ZOLPIDEM AND DIAZEPAM ON RECURRENT INHIBITION AND LONG-TERM POTENTIATION IN RAT HIPPOCAMPAL SLICES

We used the CA1 region of rat hippocampal slices to compare the effect s of non-benzodiazepine zolpidem, which binds preferentially to the om ega(1) sites of gamma-aminobutyric acid A (GABA(A)) receptors, and of benzodiazepine diazepam, which binds equipotently to the omega(1) and omega(2) sites, on the hippocampal inhibitory mechanism and on long-te rm potentiation (LTP), a possible cellular mechanism for memory. First , 1 mu M diazepam had an enhancing effect on recurrent inhibition by a lveus stimulation of orthodromically-induced population spikes, but 1 mu M zolpidem had no significant effect. Second, 1 mu M diazepam block ed LTP induction of the population spikes, whereas 1 mu M zolpidem had no such effect. Only at a higher concentration of 10 mu M, zolpidem h ad a significant effect on recurrent inhibition and LTP. These finding s suggest that only the omega(2) sites are mainly involved in modulati on of the hippocampal inhibitory mechanism and LTP, and that the low a ffinity of zolpidem for the omega(2) sites may account for less memory impairment caused by zolpidem than by benzodiazepines. (C) 1998 Elsev ier Science Ireland Ltd.