Objective: Post-traumatic stress disorder (PTSD) often co-occurs with alcohol use disorder (AUD), leading to exacerbated symptoms and poorer treatment outcomes. Despite the significant comorbidity, therapeutic options remain limited. This study aimed to evaluate the efficacy of Minocycline, a second-generation tetracycline with anti-inflammatory and neuroprotective properties, in a comorbid model of PTSD and AUD in Wistar rats. Methods: A study involving 48 male Wistar rats aged 6-8 weeks was conducted to investigate the effects of Minocycline and Fluoxetine on predator scent-induced anxiety. The rats were divided into control, disease control, Fluoxetine, and Minocycline groups, with two-bottle choice paradigms for alcohol and sucrose consumption. Predator scent stress was induced using cat urine, and anxiety was assessed using behavioral tests including Elevated Plus Maze (EPM) and Open Field Test (OFT). Serum cortisol levels and brain IL-1α were measured to evaluate stress and inflammation. Results: Study showed a significant reduction in ethanol consumption in rats treated with Minocycline compared to the disease control group, indicating an ameliorating effect on anxiety and alcohol use disorder. Behavioral tests revealed decreased anxiety-like behavior and freezing responses in Minocycline-treated animals compared to controls. Additionally, Minocycline administration led to reduced serum cortisol levels and brain IL-1α levels, suggesting modulation of stress response and neuroinflammation.