Brain insulin resistance has been pointed to as a possible link between diabetes and neuropsychiatric disorders; therefore, therapeutic approaches using anti‐diabetic drugs to improve insulin levels or signaling could prevent type 1 (T1D) and type 2 diabetes mellitus (T2D)‐induced brain dysfunction. The present study aimed to determine whether metformin exerts beneficial effects on metabolic and neurobehavioral outcomes in the streptozotocin (STZ)‐induced T1D model and western diet (WD)‐induced obesity model in male Swiss mice. T1D was induced by intraperitoneal injection of STZ (50 mg/kg, for five consecutive days). The animals were then treated daily with saline or metformin (200 mg/kg/day, oral gavage), and a battery of tests recapitulating different neurobehavioral anomalies related to anxiogenic/depressive‐like phenotype was conducted after 18 days. WD‐induced obesity was modeled in mice by high‐fat and high‐fructose diet (HFFD) feeding for 15 days. In the sequence, control and diet‐induced obesity mice were treated daily with saline or metformin (200 mg/kg/day), and a battery of behavioral tests was performed after 17 days. STZ injection and WD feeding induced metabolic and neurobehavioral impairments in mice. Remarkably, metformin improved the metabolic and neurobehavioral parameters in WD‐induced obesity mice. Moreover, metformin ameliorated STZ‐induced neurobehavioral deficits while it failed to improve the associated metabolic impairments. The beneficial effects of metformin in STZ‐induced neurobehavioral impairments were not mediated by improving peripheral insulin signaling. Our results suggest that conventional diabetes treatment could be repurposed to simultaneously improve neurobehavioral symptoms and diabetes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.