EFFECTS OF METRIFONATE, A CHOLINESTERASE INHIBITOR, ON LOCAL CEREBRALGLUCOSE-UTILIZATION IN YOUNG AND AGED RATS

The effects of the centrally acting anticholinesterase metrifonate (MF T) and its metabolite dichlorvos (2,2-dichlorovinyl dimethyl phosphate : DDVP) on local cerebral glucose utilization (LCGU) have been studied in 3- and 27-month-old rats, using the autoradiographic [C-14]deoxygl ucose technique. In 3-month-old rats, MFT (80 mg/kg i.p.) increased LC GU significantly in 17 of the 54 regions studied, including insular, c ingulate, and temporal cortices, ventral hippocampus, thalamus, latera l habenula, substantia nigra, and superior colliculus. In these region s, the average MFT-induced increase in LCGU was 23% above control. The average hemispheric LCGU increased by 10% (p < 0.01). DDVP (5 mg/kg) increased LCGU in 19 regions (average increase 26%). The average hemis pheric LCGU increased by 9% (p < 0.01). Regional distributions of MFT- and DDVP-induced increases in LCGU were similar and overlapped the di stribution of the acetylcholinesterase activity. In 27-month-old rats, MFT was active in 18 regions (average increase 25%). The whole-brain mean LCGU increased by 10% (p < 0.01). MFT compensated for the age-rel ated hypometabolism in some brain areas including insular, temporal, a nd retrosplenial cortices, substantia nigra, and superior colliculus. The effects of MFT on LCGU were preserved in old rats, at variance wit h other anticholinesterases (tacrine, physostigmine), which are less a ctive in the aged rat brain.