COMPARISON OF CHOLINERGIC DRUG EFFECTS ON REGIONAL BRAIN GLUCOSE CONSUMPTION IN RATS AND HUMANS BY MEANS OF AUTORADIOGRAPHY AND POSITRON EMISSION TOMOGRAPHY

Cholinergic mechanisms have been extensively studied in animals and ha ve been implicated in the pathogenesis of human disorders such as Alzh eimer's disease. However, few investigations have directly evaluated t he validity of extrapolating the results of animal studies to humans. As a component of a continuing examination of the contribution of chol inergic deficits to the alterations in brain metabolism that occur in Alzheimer's disease, we have compared the effects of scopolamine and p hysostigmine on regional brain energy metabolism in both rats and huma ns, using a common region of interest atlas. In Alzheimer's patients a nd in rodents, physostigmine increased glucose metabolism in several r egions (e.g. thalamus) and decreased it in others. Overall, there was a significant positive correlation for the effects of physostigmine in the nineteen brain regions studied in both species (r=0.51, P < 0.05) . In normal humans, scopolamine induced a metabolic increase in most b rain regions except in the thalamus. Outside this structure, the regio nal effects of scopolamine were significantly and negatively correlate d (r=-0.58, P < 0.01) between rat and human. These results suggest tha t: (1) cholinergic mechanisms have a similar anatomic distribution in both species, (2) muscarinic receptor-mediated cholinergic effects cou ld predominate outside the thalamus, (3) muscarinic mechanisms are inh ibitory in humans but are more complex and possibly excitatory in rats , (4) nicotinic stimulatory effects are found in the thalamus of both species, and (5) physostigmine, but not scopolamine, alters glucose co nsumption similarly in both species.