Intracortical AF64A: memory impairments and recovery from cholinergic hypofunction.
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.
Mouton
P R
PR
Department of Biology, University of South Florida, Tampa 33620.
Meyer
E M
EM
Arendash
G W
GW
D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D001388:Aziridines / Q000008:administration & dosage* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001388:Aziridines; C044894:ethylcholine aziridinium; D002794:Choline; D000109:Acetylcholine