The Behavioral and Neuroinflammatory Impact of Ketamine in a Murine Model of Depression and Liver Damage.
International journal of molecular sciences – April 10, 2025
Source: PubMed
Summary
Ketamine shows promise in treating depression even when liver problems are present - a crucial finding for millions affected by both conditions. In mice with fatty liver disease (NAFLD) and depression-like symptoms, ketamine effectively reduced depressive behaviors and anxiety, particularly in older subjects. The treatment improved social interaction and mood without worsening liver health, though memory benefits were limited in animals with liver damage. These results suggest ketamine could be valuable for patients dealing with both depression and liver conditions.
Abstract
Non-alcoholic fatty liver disease (NAFLD) has been associated with depression and inadequate response to antidepressants. While ketamine has demonstrated efficacy in treating depression, its impact on pre-existing liver injury and depression remains unclear. This study aimed to evaluate the effects of ketamine treatment in a murine model of depression and liver damage, considering age-related differences. Young and aged male C57BL/6N mice were submitted to chronic unpredictable mild stress (CUMS) and methionine-choline-deficient (MCD) diet to induce depressive-like behavior and NAFLD. Behavioral testing (sucrose preference test, open field test, novel object recognition test, Crawley's sociability test) were used to assess ketamine's (50 mg/kg) effect on behavior. Hepatic ultrasonography was utilized to evaluate liver status. The cortical and hippocampal NeuN+, GFAP+, and Iba1+ signals were quantified for each animal. Ketamine administration proved effective in relieving anhedonia and anxiety-like behavior, regardless of liver damage. Although ketamine treatment did not improve memory in animals with liver damage, it enhanced sociability, particularly in aged subjects. The acute administration of ketamine did not affect the severity of liver injury, but seems to affect astrogliosis and neuronal loss. Although animal models of depression only replicate certain clinical features of the condition, they remain valuable for evaluating the complex and varied effects of ketamine. By applying such models, we could demonstrate ketamine's therapeutic versatility, and also indicate that responses to the treatment may differ across different age groups.