EFFECTS OF BIFEMELANE ON MUSCARINIC RECEPTORS AND CHOLINE-ACETYLTRANSFERASE IN THE BRAINS OF AGED RATS FOLLOWING CHRONIC CEREBRAL HYPOPERFUSION INDUCED BY PERMANENT OCCLUSION OF BILATERAL CAROTID ARTERIES

Cerebral hypoperfusion was chronically induced in aged rats via perman ent bilateral occlusion of common carotid arteries (2VO). Marked reduc tion of the B-max value of the muscarinic receptors (mAChR) in both th e cortex and striatum and the V-max value of choline acetyltransferase (ChAT) activity in the cortex, hippocampus and striatum were observed as compared with those of control aged rats. No significant changes i n mAChR and ChAT activity were observed between young control rats and young 2VO rats. One month post-surgery in aged rats, daily doses of b ifemelane (10 mg/kg) or aniracetam (50 mg/kg) were administered orally over a 4-week period. Administration of bifemelane significantly incr eased B-max values and decreased apparent Kd values for H-3-quinuclidi nyl benzilate (QNB) in mAChR in the striatum. Chronic administration o f bifemelane or aniracetam also enhanced CkAT activity in the cortex, hippocampus and striatum. In particular, administration of bifemelane resulted in a significant increase in V-max values of ChAT in all thre e brain regions, while no significant change in K-m values for ChAT wa s observed. These results suggest that bifemelane is responsible for t his activity, thereby enhancing the functioning system of CNS choliner gic neurons of cerebral hypoperfused aged rats.