Minocycline inhibits microglial activation and mitigates compulsive and anxiety-like behaviors induced by a high-refined carbohydrate diet in male BALB/c mice.

Consumption of a high-carbohydrate (HC) diet, which is commonly associated with obesity, has been linked to anxiety-like and compulsive behaviors. This association is predominantly attributed to chronic low-grade inflammation, which affects both the peripheral tissues and the central nervous system. Microglial cells, which are essential for neuroinflammation, exacerbate psychiatric disorders, such as depression and anxiety. Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective properties by modulating the activation of microglia. This study aimed to investigate whether minocycline alleviates compulsive and anxiety-like behaviors, as well as inflammatory responses, in mice fed an HC diet. Male BALB/c mice were fed standard chow (control diet) or high-carbohydrate (HC) diet for 12 weeks. Minocycline (50 mg/kg) was administered for 7 days (intraperitoneally) or 15 days (orally, by gavage) before the end of the dietary protocol. Behavioral assessments using the Marble Burying (MB) and novelty suppressed feeding (NSF) tests were conducted 24 h after the end of the diet. Brain, adipose tissue, and serum samples were analyzed for morphological and biochemical changes. Minocycline treatment for 15 days, but not for 7 days, reversed compulsive and anxiety-like behaviors. It also reduced microglial activation in the prefrontal cortex and the hippocampus. Despite these central effects, minocycline showed a limited influence on the peripheral metabolic parameters altered by the HC diet. This study highlights the role of microglial cells in HC diet-related behavioral changes in male mice and indicates that minocycline exerts central anti-inflammatory effects. These findings warrant further studies to confirm their relevance in other animal models and their potential applicability to anxiety and obsessive-compulsive disorders in humans.