Potentiation of muscimol-induced long-term depression by benzodiazepines but not zolpidem

Zolpidem is a rapid-onset, short-duration, quickly eliminated imidazopyridine hypnotic. It has been suggested that zolpidem may produce less memory and cognitive impairment than benzodiazepines (BZs) due to its low binding affinity for BZ receptor subtypes found in areas of the brain that are involved in learning and memory, in particular the hippocampus, A novel protocol for inducing long-term synaptic depression through activation of gamma-aminobutyric acid (GABA(A)) receptors in the hippocampal slices has been recently reported. The authors used the CA1 region of rat hippocampal slices to compare the effects of classic BZs, which bind equipotently to BZ1 and BZ2 sites, and of nonbenzodiazepine zolpidem, which binds preferentially to the BZ I sites of GABAA receptors, on the GABA(A)-induced long-term depression (LTD), a possible cellular mechanism for their different cognition-impairment profile, Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that diazepam and cholordiazepoxide at concentrations of 10 and 20 muM, which did not have any effect themselves on the population spike, potentiate the ability of muscimol to induce LTD, whereas zolpidem at concentrations of 10 and 20 muM failed to potentiate muscimol-induced LTD. The results suggest that the potentiation of muscimol-induced LTD by diazepam or chlordiazepoxide and the lack of this effect by zolpidem may explain their different cognition impairment profiles, (C) 2002 Elsevier Science Inc. All rights reserved.