Effect of metrifonate on extracellular brain acetylcholine and object recognition in aged rats

• Published in: European journal of pharmacology Vol. 325; no. 2; pp. 173 - 180
• Main Authors: Scali, Carla, Giovannini, Maria Grazia, Bartolini, Luciano, Prosperi, Costanza, Hinz, Volker, Schmidt, Bernard, Pepeu, Giancarlo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.05.1997; Elsevier
• Subjects: Acetylcholine; Acetylcholine - metabolism; Administration, Oral; Aging; Aging - psychology; Alzheimer Disease - drug therapy; Alzheimer Disease - psychology; Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cholinesterase inhibitor; Cholinesterase Inhibitors - administration & dosage; Cholinesterase Inhibitors - pharmacology; Cholinesterase Inhibitors - toxicity; Extracellular Space - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Male; Medical sciences; Memory - drug effects; Memory - physiology; Memory Disorders - drug therapy; Metrifonate; Neuropharmacology; Neuroprotective agent; Object recognition; Pharmacology. Drug treatments; Rats; release; Trichlorfon - administration & dosage; Trichlorfon - pharmacology; Trichlorfon - toxicity; Aging; Acetylcholine; Object recognition; Cholinesterase inhibitor; Metrifonate; Cerebral cortex; Senescence; Rat; Central nervous system; Esterases; Cognition; Mechanism of action; Enzyme; Rodentia; Enzyme inhibitor; Neuroprotective agent; Pattern recognition; Extracellular; Biological activity; Young animal; Cholinesterase; Carboxylic ester hydrolases; Vertebrata; Mammalia; Aged animal; Neurotransmitter; Hydrolases; Hippocampus; Brain (vertebrata); Cholinergic transmission
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)00128-3

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.