Effects of intracerebroventricular injection of AF64A on learning behaviors in rats.
The effects of intracerebroventricular (ICV) injection of ethylcholine aziridinium ion (AF64A) (3 nmole/2 microliter, each lateral ventricule), a putative selective cholinotoxin, on learning behaviors and choline acetyltransferase (ChAT) activity were studied in rats. AF64A-treated rats (AF64A-rat) exhibited deficient performance in a passive avoidance task and a delayed alternation task in the T-maze, but demonstrated superior avoidance response in a two-way shuttle avoidance task. These changes in learning behaviors were associated with the selective decrease of hippocampal ChAT activity. Physostigmine (0.1 mg/kg, i.p.) significantly improved the retention latency of AF64A-rats in the passive avoidance task. AF64A-rats receiving physostigmine (0.2 mg/kg, i.p.) exhibited a slight but not significant improvement of performance in the delayed alternation task in the T-maze. These findings suggested that ICV injection of AF64A may be useful for producing an experimental amnesia model with hippocampal cholinergic hypofunction like Senile dementia of the Alzheimer type (SDAT), if appropriate learning tests are selected.
Nakahara
N
N
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan.
Iga
Y
Y
Mizobe
F
F
Kawanishi
G
G
D000544:Alzheimer Disease / Q000188:drug therapy / Q000523:psychology; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001388:Aziridines / Q000008:administration & dosage*; D001389:Azirines / Q000008:administration & dosage*; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D007858:Learning / Q000187:drug effects*; D008297:Male; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001388:Aziridines; D001389:Azirines; D010830:Physostigmine; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D002794:Choline