EFFECT OF RESVERATROL ON SOCIAL INSTABILITY STRESS-INDUCED DEPRESSION-LIKE BEHAVIOURS IN FEMALE WISTAR RATS: GUT MICROBIOME, ENDOCRINE, NEUROTROPHIN, AND NEUROTRANSMITTER PATHWAYS

Depression is a common psychiatric disorder that occurs twice as often in females as in males, with an extreme global economic burden. Although there are known effective treatments for depression, over 75% of people in low- and middle-income countries receive no treatment. A major barrier is the high cost of existing drugs. Hence, there is a need to find cheaper and accessible alternative treatments. Probiotics, e.g., polyphenols, are nutritional, microbiota-targeted compounds being investigated as treatment alternatives. They offer supplementary benefits by reducing inflammation and modulating the gut-brain axis. Thus, this study explored how resveratrol influences gut-brain axis interactions and its therapeutic potential in stress-induced depressive states. Thirty-five adult female Wistar rats (180 & 220 g) were acclimatised for 3 weeks in plastic cages with feed and water ad libitum. They were exposed to social instability stress. Elevated zero and Crawley’s maze tests were carried out before and after induction of depression-like behaviours, as well as after treatment. Drugs were administered orally, once daily for 8 weeks. Rats were euthanised, faecal and blood samples were collected for biochemical analyses. The results showed that rats in the resveratrol-treated group exhibited significant (p < 0.05) increases in the percentage of time spent in the open and sociability index compared to the other groups. They also showed a significant (p<0.05) increase in weight and faecal long-chain fatty acids, a decrease in CRH and ACTH levels, but no effect on serum serotonin and GDNF. In conclusion, resveratrol reduced anxiety-like behaviour, and improved social interaction.