Amnesic trace locked into the benzodiazepine state of memory

Rats were trained in a food-rewarded lever-pressing task until they could complete an FR10 requirement within the first 120 s of the session, and were tested for the retention of this response requirement after having reached this criterion. The pharmacological treatment instituted at the time of tests was either the same as or different from that used during acquisition. In this state-dependency (StD) procedure, saline-to-drug as well as drug-to-saline state changes produced robust failures to transfer with chlordiazepoxide (CDP) and also with yohimbine. Diazepam substituted for, while Ro 15-1788 antagonised, CDP; none of several non-benzodiazepine compounds substituted for CDP. Neither food deprivation nor extensive overtraining after CDP prevented the failure of transfer when animals were tested for drug-to-saline transfer. Another series of experiments evaluated the effects of CDP and diazepam in a rat conflict procedure. The doses at which CDP and diazepam produced anti-conflict effects were similar to those at which failure to transfer occurred in saline-to-drug state changes, and higher than those at which such failure occurred in drug-to-saline state changes. With benzodiazepines, StD of memory retrieval conceivably constitutes a parsimonious explanation of the anxiolytic and untoward (amnesic, drug dependence) actions of these drugs.