Effect of metformin on morphine induced working memory defects in rats

Chronic administration of morphine leads to structural changes in the brain. Some studies have shown the antioxidant and neuroprotective effects of metformin. The aim of this study was to investigate the effect of metformin on working memory in morphine-treated rats.

In this study, 40 male Wistar rats were used. Animals were divided into 5 experimental groups (8 rats in each group): 1- control (animals received saline, orally for 7 days); 2- Metformin (animals received 50 mg/kg metformin, orally for 7 days); 3- Morphine (animals received subcutaneous morphine 10 mg/kg twice a day for 7 days); 4 and 5- Morphine + metformin, animals received morphine and metformin (5 or 50 mg/kg, orally) daily for 7 days. To evaluate the working memory, Y-maze spontaneous alternation test was used. Lipid peroxidation was assessed by measuring level of Malondialdehyde (MDA) in hippocampal tissue of rats.

Morphine administration resulted in working memory deficits and increased MDA levels compared to the control group (p < 0.001). Metformin alone, at the doses used, had no effect on the working memory but the dose of 50 mg/kg significantly improved working memory (p < 0.01) and decreased MDA level (p < 0.05) of the morphine-treated rats.

Metformin can improve morphine-induced deficits in the working memory of rats.