Metformin reaches reward-circuit brain regions in rats and blocks cocaine sensitization in males only
- Metformin, an antidiabetic drug being repurposed for addiction, was given to rats in drinking water for one to several weeks, and its levels were then measured by mass spectrometry in blood and in striatal and prefrontal tissue.
- Brain levels were comparable across the sampled regions in both sexes. Rats cut their water intake as concentration rose, so a stronger solution did not necessarily mean higher plasma or brain levels.
- Free access to metformin water prevented cocaine locomotor sensitization in males only, which the authors take to suggest a sex difference in how the drug distributes across the blood–brain barrier.
💡 Points Based on the abstract
Nice to see actual brain levels, since most repurposing work just assumes metformin gets in. But drinking-water dosing is a messy way to define exposure: intake falls at higher doses, and rats drink nocturnally, so peak and trough are uncontrolled. Tissue totals also don't give free, intracellular or mitochondrial concentrations, which is where AMPK or complex I effects would happen. Next: gavage or osmotic pump with a dose-response in both sexes.