Now a popular fad diet, the ketogenic diet (KD) is a high-fat, low-carb diet that for decades has been used for treatment of intractable epilepsy. Recent therapeutic applications of KD in animal models include treatment of dementia, obsessive-compulsive disorder, and autism. These disorders are associated with stereotypic behaviors (repetitive, invariant behaviors with no apparent function) that are life-impairing and stigmatizing. However, little is known about their underlying mechanisms and no effective pharmacological treatments are available. Here, we present a novel application of KD to reduce stereotypic behavior in an inbred strain of mice (FVBN/J) that displays a prominent repetitive circling behavior. In Experiment 1, we reduced overall stereotypic behavior in aged (18 months) mice with 3-week administration of KD. In Experiment 2, adult (6-8 months) females were paired such that a “spinner” mouse and a non-spinning control mouse were housed together (N=14 cages). Using an ABAB design, we compared stereotypic behavior between assessment periods on normal food diet and on KD. These data show an interaction between time and diet on stereotypic behavior. Following Golgi-Cox histochemistry, the density of dendritic spines in the dorsal and ventral striatum were investigated as one potential neurobiological mechanism for these effects
