A ketogenic diet diminishes behavioral responses to cocaine in young adult male and female rats

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Ketogenic diets (KDs) are high fat, low carbohydrate formulations traditionally used to treat epilepsy; more recently, KDs have shown promise for a wide range of other neurological disorders. Drug addiction studies suggest that repeated exposure to drugs of abuse, including cocaine, results in a suite of neurobiological changes that includes neuroinflammation, decreased glucose metabolism, and disordered neurotransmission. Given that KDs positively regulate these factors, we addressed whether administration of a KD has potential as a novel therapy for drug addiction. In this study, male and female Sprague-Dawley rats were placed on a KD or a control diet (CD), beginning at five weeks of age and continuing through the end of behavioral testing. Three weeks after initiation of dietary treatments, rats received daily i.p. injections of cocaine (15 mg/kg) or saline vehicle for one week, were drug free for a subsequent week, and then all animals received a final challenge injection of 15 mg/kg cocaine. In the absence of cocaine injections, stereotyped locomotor responses were minimal and were unaffected by dietary treatment. In contrast, both males and females fed a KD exhibited decreased cocaine-induced stereotyped responses as compared to CD-fed rats. The sensitization of ambulatory responses was also disrupted in KD-fed rats. These results suggest that KDs directly impact dopamine-mediated behaviors, and hence may hold potential as a therapy for drug addiction.