Investigating the Effect of Caffeine on the Effectiveness of Crocin in Improving Behavioral Symptoms and Brain Tissue Changes in the Hippocampus in the Post-Traumatic Stress Model in Rats.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition. Although crocin has shown potential in reducing stress-related symptoms, its low bioavailability limits its effectiveness. Caffeine may enhance the bioavailability of various compounds by modulating liver enzymes. This study examined whether caffeine could improve crocin's efficacy in a rat model of PTSD.

MATERIALS AND METHODS: Male Wistar rats (8-10 weeks old) were divided into five groups: control, PTSD, crocin-treated, caffeine-treated, and crocin + caffeine-treated. PTSD was induced using repeated foot shocks, followed by 7 days of treatment. Behavioral assessments were performed using the elevated plus maze and shuttle box tests. Serum corticosterone levels were measured as a biochemical marker of anxiety, and histological evaluation of the hippocampus was conducted using Cresyl Violet and Golgi-Cox staining.

RESULTS: The combination treatment significantly reduced serum corticosterone levels compared to either compound alone (P < 0.01). Behavioral improvements-including increased grooming, time spent in open arms, and reduced freezing latency-were most pronounced in the crocin + caffeine group. Histological analysis also revealed reduced neuronal damage in this group.

CONCLUSIONS: We concluded that a combination of crocin and caffeine could improve the efficacy of crocin given alone. These findings indicate that caffeine can help further enhance the neuroprotective efficacy of crocin in this model.