Abstract |
The long-term effects of intracortical AF64A ( ethylcholine mustard aziridinium ion) treatment on presynaptic cortical cholinergic markers and cognitive function in the rat were investigated. Two 1.0 microliter infusions of AF64A (1 nmole/microliter) or vehicle were placed bilaterally into the fronto-parietal cortex. At 3 weeks postinfusion, AF64A-treated animals were found to be deficient in passive avoidance memory retention. During weeks 4 through 10, AF64A-treated animals were markedly deficient in the extinction (memory) phase, but not the acquisition (learning) phase of 2-way active avoidance behavior. Cortical acetylcholine synthesis and high-affinity choline uptake were significantly decreased in AF64A-treated animals at 24 hours, 3 weeks, and 10 weeks following infusion. At 6 months after AF64A treatment, however, cortical cholinergic markers were not reduced compared to controls. These data indicate that memory deficits are observed during a period of cortical cholinergic hypofunction induced by cortical AF64A infusions and that a recovery from such hypofunction occurs by 6 months after these infusions.
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Authors | P R Mouton, E M Meyer, G W Arendash |
Journal | Pharmacology, biochemistry, and behavior
(Pharmacol Biochem Behav)
Vol. 32
Issue 4
Pg. 841-8
(Apr 1989)
ISSN: 0091-3057 [Print] United States |
PMID | 2798533
(Publication Type: Journal Article)
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Chemical References |
- Aziridines
- ethylcholine aziridinium
- Choline
- Acetylcholine
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Topics |
- Acetylcholine
(metabolism)
- Alzheimer Disease
- Animals
- Avoidance Learning
(drug effects, physiology)
- Aziridines
(administration & dosage, pharmacology)
- Biological Transport
(drug effects)
- Cerebral Cortex
(drug effects, metabolism)
- Choline
(administration & dosage, pharmacokinetics, pharmacology)
- Disease Models, Animal
- Memory
(drug effects, physiology)
- Rats
- Rats, Inbred Strains
- Time Factors
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