Major depression is linked to cognitive, emotional, and physiological alterations, experimentally modeled in rodents through 3 months of social isolation. This study evaluated the effect of metformin (100mg/kg/day orally) on spatial memory, anxiety, anhedonia, and physiological parameters in male Sprague-Dawley rats. We used three groups (n=17): Isolated Water (untreated, n=6), Isolated Met (n=5), and Social (control, n=6).
Depression-like behavior was assessed via the marble burying, sucrose preference, and forced swim tests. Episodic memory was evaluated using Spontaneous Location Recognition (SLR) and the Barnes Maze.
Metformin reduced anxious behavior (marble burying), regulated food intake and weight, and reversed anhedonia (sucrose preference similar to Social group, p<0.01). However, it did not alter depressive behavior in the forced swim test. In the SLR, the Isolated Met group showed a significant preference for the moved object (p<0.01), indicating hippocampal recovery, unlike the Isolated Water group. Yet, in the Barnes Maze, no significant improvement was observed in the probe trial; latency and errors did not differ from the untreated group.
These results suggest metformin has a positive effect on emotional behavior, spontaneous spatial exploration, and physiological parameters, although it does not completely restore goal-directed spatial memory. This positions metformin as a potential therapeutic target for mood disorders.