Intrahippocampal injections of benzodiazepine and muscimol impair working memory but not reference memory of rats in the three-panel runway task.

In a three-panel runway task, the benzodiazepine chlordiazepoxide at 3.2 and 10 mg/kg i.p. significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in a test of working memory, but it had no effect on errors in a test of reference memory. This effect of 10 mg/kg chlordiazepoxide on working memory was blocked by the benzodiazepine receptor antagonist flumazenil at 10 mg/kg. Intrahippocampal injection of chlordiazepoxide at 10 and 32 micrograms/side significantly increased the number of working memory errors. This effect of intrahippocampal chlordiazepoxide (32 micrograms/side) was attenuated not only by flumazenil at 10 mg/kg but also by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline at 3.2 mg/kg. Intrahippocampal injection of the GABAA receptor agonist muscimol at 100 and 320 ng/side also significantly increased working memory errors. Neither chlordiazepoxide nor muscimol affected the number of reference memory errors when injected into the hippocampus at doses up to 32 micrograms/side or 320 ng/side, respectively. These results suggest that activation of the GABAA/benzodiazepine receptor complex in the hippocampus impairs working memory, but does not affect reference memory.