Sustained effect of metrifonate on cerebral glucose metabolism after immunolesion of basal forebrain cholinergic neurons in rats

To evaluate the influence of cholinergic projections from the basal forebrain on brain metabolism, we measured the cerebral metabolic rate of glucose (CMR(glu)) after unilateral lesioning of cholinergic basal forebrain neurons with the immunotoxin 192 IgG-saporin. CMR(glu) was determined in 24 cortical and 13 sub-cortical regions using the [C-14]2-deoxy-D-glucose technique of Sokoloff. Average hemispheric CMR(glu) decreased by 7% (P < 0.02) and 5% (P ( 0.05), 7 and 21 days after lesion, respectively. Regional effects were restricted to parietal and retrosplenial cortices, lateral habenula and the basal forebrain. We have previously shown that metrifonate increased CMR(glu) in intact rats. In lesioned rats, metrifonate (80 mg/kg, i.p.) was still active bur the metabolic activation was reduced in terms of both the average hemispheric CMR(glu) and the number of regions significantly affected. Although it is reduced, the sustained effect of metrifonate in lesioned rats makes an argument for the use of this compound as treatment of cholinergic deficit in Alzheimer's disease. (C) 2000 Elsevier Science B.V. All rights reserved.