title: Effect of metrifonate on extracellular brain acetylcholine and object recognition in aged rats.
abstract: 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.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Scali
authors.forename: M G
authors.initials: MG
authors.lastname: Giovannini
authors.forename: L
authors.initials: L
authors.lastname: Bartolini
authors.forename: C
authors.initials: C
authors.lastname: Prosperi
authors.forename: V
authors.initials: V
authors.lastname: Hinz
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.forename: G
authors.initials: G
authors.lastname: Pepeu
mesh_terms: 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
chemical_list: D002800:Cholinesterase Inhibitors; D014236:Trichlorfon; D000109:Acetylcholine