Diazepam induces retrograde facilitation of object recognition and object location memory in male mice

Abstract

Benzodiazepines are widely prescribed for patients suffering from anxiety and insomnia. Although amnesic effects of benzodiazepines are commonly known as side effects, it has also been reported that these drugs improve memory for information learned before drug intake, a phenomenon called retrograde facilitation. However, the retrograde effects of benzodiazepines on cognitive performances in rodents remain controversial. It should be considered that studies on diazepam-induced retrograde facilitation in humans have been conducted using a recall paradigm focused on short-term memory, whereas these studies in rodents have been conducted using memory tasks that mainly target long-term memory and/or require negative or positive reinforcers. In the current study, we investigated whether diazepam, a benzodiazepine, induces retrograde facilitation for object recognition memory and spatial memory in mice, using a novel object recognition test and an object location test, respectively. These tests are available for short-term memory and do not require any reinforcer. The mice treated with diazepam retained object recognition memory for at least 180 min and spatial memory for at least 150 min. In contrast, vehicle-treated control mice retained object recognition memory for 120 min but not 150 min or longer, and spatial memory for 90 min but not 120 min or longer. These data clearly demonstrated diazepam-induced retrograde facilitation for both object recognition and spatial memories in mice. The present study is expected to contribute to the elucidation of the neural basis of retrograde facilitation.