METABOLIC RESPONSE TO TACRINE (THA) AND PHYSOSTIGMINE IN THE AGED RAT-BRAIN

The effects of the centrally acting anticholinesterases tacrine (tetra hydroaminoacridine, THA) and physostigmine (PHY), on local cerebral gl ucose utilization (LCGU) have been studied in 27-month-old rats, using the autoradiographic [C-14]deoxyglucose technique. THA (10 mg/kg i.p. ) increased LCGU significantly in 13 of the 54 regions studied (24%) i ncluding insular, parietal, temporal, and retrosplenial cortices, sept ohippocampal system, thalamus, lateral habenula, and superior collicul us. In these regions, the average THA-induced increase in LCGU was 24% above control. The whole brain mean LCGU was not significantly increa sed. PHY (0.5 mg/kg) increased LCGU in 18% of the regions (average ele vation, 23%), The whole brain mean LCGU increased by 7% (p < 0.05). Th e regional distributions of THA- and PHY-induced increases in LCGU wer e extremely similar and overlapped the distribution of the M(2) muscar inic receptors and that of acetylcholinesterase activity, suggesting t hat the major effects of THA and PHY on LCGU result from their anticho linesterase action, As compared to those of 3-month-old rats, both the number of regions affected and the amplitude of the metabolic activat ion were significantly less in aged rats. However, the drugs were stil l active in old rats and compensated for the age-related hypometabolis m in some brain areas.