PREVENTIVE EFFECTS OF BIFEMELANE HYDROCHLORIDE ON DECREASED LEVELS OFMUSCARINIC ACETYLCHOLINE-RECEPTOR AND ITS MESSENGER-RNA IN A RAT MODEL OF CHRONIC CEREBRAL HYPOPERFUSION

Changes in muscarinic acetylcholine receptor (mACh-R) binding and musc arinic cholinergic ml receptor (ml-R) mRNA levels were determined in a rat model of cerebral hypoperfusion in which hypoperfusion was induce d by permanent bilateral occlusion of the common carotid arteries. Aft er 6 weeks of hypoperfusion, mACh-R binding activity was significantly reduced in the frontal cortex (79.0%, P < 0.01), striatum (74.2%, P < 0.01) and hippocampus (78.6%, P < 0.01), and the ml-R mRNA levels in the frontal cortex (86.6%, P < 0.05) and striatum (89.4%, P < 0.05) co mpared with sham-operated control. Repeated administration of bifemela ne hydrochloride (15 mg/kg/day, p.o., once a day from the day of opera tion for 6 weeks) prevented the hypoperfusion-induced loss of mACh-R b inding and ml-R mRNA levels above described. Since the central choline rgic systems play an important role in learning and memory, these find ings suggest that bifemelane hydrochloride is useful to treat and/or p revent vascular dementia which is closely related to cerebral hypoperf usion.