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Brain lesions and delayed water maze learning deficits after intracerebroventricular spermine
1University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia. conway@austin.unimelb.edu.au
Abstract:
The effects of spermine on the acquisition and retention of spatial learning in the Morris water maze were studied. Spermine 25 and 125 nmol i.c.v. did not alter the ability of rats to find a hidden platform in the water maze when administered before training over 5 days. However, the inhibitory effect of the benzodiazepine, diazepam (3 mg/kg i.p., 30 min prior to training), on path length to target was markedly potentiated by the higher dose of spermine, consistent with spermine acting as a functional antagonist at the NMDA receptor. This drug combination did not affect performance on visible platform trials. Administration of doses of 125 and 250 nmol (but not 62.5 nmol) of spermine i.c.v. in the week prior to training (daily for 5 days) dose-dependently inhibited subsequent learning of a platform position in the absence of drug. These higher doses of spermine produced neuronal loss and increased [3H]PK11195 binding indicating microglial activation predominantly in the hippocampus and to a lesser extent in the striatum, septum, thalamus and amygdala. Spermine 125 nmol i.c.v. (daily for 7 days) also abolished retention of a previously learned platform position when administered in an interval between training and retention testing. The inhibitory effects of spermine 125 nmol i.c.v. (daily for 7 days) on subsequent spatial learning were not antagonised by concomitant administration of 30 nmol dizocilpine. These results demonstrate that spermine produces a delayed neurotoxic effect in particular neuronal populations in the brain that selectively impair spatial learning and recall.
Insights
Spermine impairs spatial learning and memory in rats, causing neurotoxicity and microglial activation. This polyamine disrupts learning and recall, particularly in the hippocampus, suggesting a delayed neurotoxic effect on specific brain populations.
Area of Science:
- Neuroscience
- Neuropharmacology
- Behavioral Neuroscience
Background:
- Spermine, a polyamine, plays roles in cellular functions.
- Its impact on cognitive processes like spatial learning requires further investigation.
Purpose of the Study:
- To investigate the effects of spermine on spatial learning acquisition and retention in rats.
- To explore the neurobiological mechanisms underlying spermine's cognitive effects.
Main Methods:
- Rats were trained and tested in the Morris water maze following intracerebroventricular (i.c.v.) administration of spermine.
- Spatial learning was assessed by measuring path length to a hidden platform.
- Neurotoxicity and microglial activation were evaluated using histological methods and radioligand binding assays.
- Interactions with diazepam and dizocilpine were examined.
Main Results:
- Spermine alone did not affect initial learning but potentiated diazepam's amnesic effects, suggesting NMDA receptor antagonism.
- Higher spermine doses administered before training dose-dependently inhibited spatial learning and induced neuronal loss with microglial activation, primarily in the hippocampus.
- Spermine administration between training and testing abolished retention of a learned task.
- Dizocilpine did not antagonize spermine's inhibitory effects on spatial learning.
Conclusions:
- Spermine exerts a delayed neurotoxic effect on specific brain regions, notably the hippocampus.
- This neurotoxicity selectively impairs spatial learning acquisition and memory recall.
- Spermine's actions may involve complex interactions with neurotransmitter systems and glial cells.