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Development of a mouse autoshaping model to test for short‐term memory impairment

Short term memory loss and memory disruption are prominent clinical symptoms in the Alzheimer's disease and other dementias. The purpose of the present study was to develop an objective mouse model of short term memory loss that can be pharmacologically manipulated to test novel compounds. To this end, we modified a rat autoshaping model (Menses et al., 2007) for mice. Male, Swiss‐Webster mice were placed within experimental chambers to measure the acquisition of nose‐poke responding in the presence of an audible tone presented on a variable‐interval schedule to earn 10 Ensure solution rewards. After the completion of the first session, mice are injected with saline or a dose of drug and returned to their home cages. One hour later, mice were returned to the chambers to measure retention of the autoshaped response. Mice injected with saline, responded faster and more accurately during the second session indicating retention of the learned response. Mice injected with NMDA noncompetitive antagonist ketamine (3.2–18 mg/kg) or scopolamine (1–10 mg/kg) failed to show a significant difference from the first and the second session without rate suppression indicating memory impairment. Future studies will examine standard and novel agents to reverse the effects of ketamine and scopolamine to further test the utility and validity of this short term memory mouse autoshaping model. (Supported by R01CA129092).