035— Working Memory and Locomotor Activity in Old and Young Mice Fed a Ketogenic Diet

The ketogenic diet (KD), a high-fat, low-carb diet, has recently been used to treat disorders associated with an inflexibility of cognitive and behavioral routines, such as dementia and autism spectrum disorder. However, there has been little investigation into how KD’s beneficial effects on cognitive behavior may change with age. Here, we show the effects of KD on performance in a working memory task and locomotor activity in young and old C57BL6/J mice. In Experiment 1, we used a Barnes Maze to assess working memory. In the Barnes Maze, mice locate an escape box under a target hole by using spatial cues. Each day the target hole is moved to a new location. We found that mice on KD performed better, indicated by shorter latencies to find the target hole. However, only the young mice on KD made fewer errors. To check for differences in activity between mice on KD and mice fed a normal diet, Experiment 2 employed a 1h locomotor test. KD increased horizontal activity in young and old mice. Thus, regardless of age, mice fed KD performed better in a working memory task and were more active. Findings may be useful for using KD as a therapy

258— Differential response to cocaine in mice exposed to stress

Exposure to trauma is a risk factor for substance use disorders. Using a mouse model of PTSD, we tested the effects of exposure to a stressor (synthetic fox pheromone: TMT) on response to cocaine. Cocaine induced locomotion and cocaine seeking behavior in a conditioned place preference (CPP) were assessed. TMT was an effective stressor, indicated by freezing behavior, which is a known fear response in mice. In both males and females, TMT-exposed mice showed a greater locomotor response to cocaine compared to control mice, resulting in the interaction between time and TMT treatment. TMT-exposed males, but not females, were overall more active than control mice. During CPP, female mice were first conditioned to associate one side of a 3-chambered arena with cocaine (10 mg/kg) and then tested in a 30-minute session of free exploration (15 minutes of cue-prime, 15 minutes of drug-prime). Time spent inside the drug-associated context was considered an indication of the rewarding properties of cocaine. Results indicated no group differences between female mice exposed to TMT and those that weren’t. Additionally, mice only displayed a preference for the cocaine-paired chamber during cue-primed testing. After receiving a cocaine-prime (10 mg/kg), mice did not continue this behavior

142 -- Working Memory, Locomotor Activity, and Neuronal Density in Old Mice Fed a Ketogenic Diet

The ketogenic diet (KD), is a high-fat, low-carb diet which has recently become popular as a way to improve memory and cognitive function. There is little research done on the benefits of KD and to what extent it benefits memory function. We modeled the effects that KD has on performance of old mice during a working memory task and locomotor activity. As a control, half of the mice were fed normal chow, while the other half were fed KD. In experiment 1, the Barnes Maze was used to assess working memory. Using spatial cues, the mouse escapes to a target hole located in the Maze, and each day the target location is changed. KD mice showed a lower latency to escape and a tendency to make fewer mistakes. To detect if there were diet-induced differences in activity, experiment 2 utilized a 1hr locomotor test at the start of the diet period (baseline) and again at the end of the diet period (KD) but found no differences between mice on KD and mice fed a normal diet. In experiment 3, we used a cresyl violet stain to assess neuronal density in regions of the brain involved in memory, that included the prefrontal cortex and hippocampus, where higher density was hypothesized to be found in KD mice. Overall, we investigated one potential mechanism for our findings that show KD improves working memory performance without affecting locomotor activity. Results support the potential for using KD as a treatment for disorders with memory impairments