Effect of metrifonate on extracellular brain acetylcholine and object recognition in aged rats.
The effects of metrifonate were investigated in 4-6- and 22-24-month-old rats. Extracellular acetylcholine levels were measured by transversal microdialysis in vivo. Baseline extracellular acetylcholine levels in the cerebral cortex and hippocampus were 42% and 60% lower, respectively, in old than in young rats. Old rats did not discriminate between familiar and novel objects. In old rats, metrifonate (80 mg/kg p.o.) brought about 85% inhibition of cholinesterase activity in the cortex and hippocampus, a 4-fold increase in extracellular acetylcholine levels in the cortex only, and restored object recognition. In young rats, metrifonate caused 75% cholinesterase inhibition in the cerebral cortex and hippocampus, a 2-fold increase in cortical and hippocampal extracellular acetylcholine levels, and no effect on object recognition. The slight cholinesterase inhibition following metrifonate (30 mg/kg) in aged rats had no effect on cortical acetylcholine levels and object recognition. In conclusion, metrifonate may improve the age-associated cholinergic hypofunction and cognitive impairment.
Scali
C
C
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Giovannini
M G
MG
Bartolini
L
L
Prosperi
C
C
Hinz
V
V
Schmidt
B
B
Pepeu
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000284:Administration, Oral; D000375:Aging / Q000523:psychology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000523:psychology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy; D051381:Rats; D014236:Trichlorfon / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
D002800:Cholinesterase Inhibitors; D014236:Trichlorfon; D000109:Acetylcholine