Effect of subchronic metrifonate treatment on cerebral glucose metabolism in young and aged rats.
The effects of subchronic administration of metrifonate, a long-lasting cholinesterase inhibitor, on local cerebral glucose utilization were assessed in 3- and 27-month old Sprague-Dawley rats, using the autoradiographic [14C]2-deoxyglucose technique. Rats were treated twice daily with metrifonate (80 or 120 mg/kg) for 3 weeks. The [14C]2-deoxyglucose experiment was performed 18 h after the last metrifonate administration. In 3-month old rats, metrifonate 80 mg/kg increased the average hemispheric cerebral glucose utilization 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 affected). In 27-month old rats, very similar effects were obtained. These results show that repeated administration of metrifonate leads to a sustained metabolic activation in rat brain, at a level comparable to the activation observed previously after a single administration of the drug.
Poindessous-Jazat
F
F
INSERM U 161, Paris, France.
Schmidt
B H
BH
Bassant
M H
MH
D000367:Age Factors; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014236:Trichlorfon / Q000008:administration & dosage / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D014236:Trichlorfon; D005947:Glucose