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Published on: December 4, 2013
Effects of metrifonate on radial arm maze acquisition in middle-aged rats
1Israel Institute for Biological Research, Department of Pharmacology, Ness-Ziona.
Abstract:
The efficacy of metrifonate, a well-tolerated cholinesterase (ChE) inhibitor, in attenuating the normal aging- and corticosterone-induced impairments of radial maze performance of rats was compared. Middle-aged Fischer 344 rats were screened for their spatial orientation performance in the Morris water escape task. Good and bad performers were selected: good performers (N= 22) were treated with subcutaneous sustained-release corticosterone pellets, resulting in hippocampal cell damage and impaired spatial orientation in the radial maze; age-induced bad performers (N = 20) were tested without additional pharmacological intervention. Metrifonate (MFT), administered daily during radial maze testing, 30 min before training, at a dose of 15 mg/kg p.o., facilitated the acquisition of the task in age-impaired rats, but not in corticosterone-impaired rats.
Insights
Metrifonate improved spatial learning in aging rats but did not benefit rats with corticosterone-induced impairments. This cholinesterase inhibitor shows potential for age-related cognitive decline.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Behavior
Background:
- Aging and stress hormones like corticosterone can impair cognitive functions, including spatial orientation.
- Cholinesterase inhibitors are a class of drugs that can enhance neurotransmission and are explored for cognitive enhancement.
Purpose of the Study:
- To compare the efficacy of metrifonate in ameliorating age-related versus corticosterone-induced spatial memory deficits in rats.
- To investigate metrifonate's effect on radial maze performance in two distinct models of cognitive impairment.
Main Methods:
- Fischer 344 rats were screened for spatial orientation using the Morris water escape task.
- Good performers received corticosterone pellets to induce impairment; age-impaired rats served as a separate group.
- Metrifonate (15 mg/kg p.o.) was administered daily before radial maze training.
Main Results:
- Metrifonate facilitated task acquisition in age-impaired rats.
- Metrifonate did not improve performance in rats with corticosterone-induced spatial memory deficits.
- Corticosterone treatment led to hippocampal cell damage and impaired spatial orientation.
Conclusions:
- Metrifonate demonstrates potential in improving age-related spatial learning deficits.
- The drug's efficacy may be specific to the underlying cause of cognitive impairment, showing limited benefit in stress-induced deficits.
