Effect of subchronic metrifonate treatment on cerebral glucose metabolism in young and aged rats

The effects of subchronic administration of metrifonate, a long-lasting cho linesterase inhibitor, on local cerebral glucose utilization were assessed in 3- and 27-month old Sprague-Dawley rats, using the autoradiographic [C-1 4]2-deoxyglucose technique. Rats were treated twice daily with metrifonate (80 or 120 mg/kg) for 3 weeks. The [C-14]2-deoxyglucose experiment was perf ormed 18 h after the last metrifonate administration. In 3-month old rats, metrifonate 80 mg/kg increased the average hemispheric cerebral glucose uti lization by 12% (P > 0.001). Significant effects were observed in 19 of the 54 regions studied, including cortical and limbic regions. The higher dose induced a larger effect (average increase 17%, 24 of the 54 regions affect ed). In 27-month old rats, very similar effects were obtained. These result s show that repeated administration of metrifonate leads to a sustained met abolic activation in rat brain, at a level comparable to the activation obs erved previously after a single administration of the drug. (C) 1998 Elsevi er Science B.V. All rights reserved.