TETRAHYDROAMINOACRIDINE AND PHYSOSTIGMINE INCREASE CEREBRAL GLUCOSE-UTILIZATION IN SPECIFIC CORTICAL AND SUBCORTICAL REGIONS IN THE RAT

The effects of the anticholinesterases tetrahydroaminoacridine (THA) a nd physostigmine on local cerebral glucose utilization (LCGU) were stu died in the conscious rat, using the autoradiographic [C-14]deoxygluco se technique. THA (5 mg/kg i.p.) increased LCGU significantly in 8 of the 43 regions studied. A higher dose of THA (10 mg/kg) produced a met abolic activation in 19 of the 43 regions. LCGU increased in cortical areas (including parietal and temporal cortices), the septohippocampal system, the thalamus, the lateral habenula, the basolateral amygdala, the superior colliculus, and the substantia nigra. Scopolamine (4 mg/ kg i.p.) reversed the THA-induced LCGU increase. Physostigmine (0.2 an d 0.5 mg/kg) increased LCGU in 15 and 22 regions, respectively. The av erage magnitude of the change induced by 0.5 mg/kg of physostigmine wa s similar to that observed after THA at 10 mg/kg, but the topography o f the effects was somewhat different. Physostigmine increased LCGU in the preoptic magnocellular area, the brainstem, and the cerebellum but not in the parietal cortex. The effects in the septohippocampal syste m were smaller than those induced by THA. The regional topography of t he LCGU increase overlapped the distribution of the M2 muscarinic rece ptors and that of acetylcholinesterase activity. These data suggest th at the major effects of THA and physostigmine on LCGU result from thei r anticholinesterase action.