Effects of chronic in vivo replacement of choline with a false cholinergic precursor.
Chronic administration to rats of a diet in which all choline is replaced by NADe, an unnatural choline analog, results in a classical hypocholinergic syndrome characterized by progressive loss of learning and memory, hyperkinesis, hyperreactivity and hyperalgesia. Discontinuation of the artificial diet results in rapid elimination of NADe from both free and phospholipid-bound pools in all tissues studied, but the behavioral effects recede more slowly and incompletely. These results are consistent with a model in which choline and NADe compete in both acetylcholine and phospholipid synthesis, resulting in selective vulnerability of cholinergic neurons. Histological studies are in progress to determine whether microanatomical changes are also consistent with this model.
Jenden
D J
DJ
Department of Pharmacology, School of Medicine, University of California, Los Angeles 90024-1735.
Russell
R W
RW
Booth
R A
RA
Knusel
B J
BJ
Lauretz
S D
SD
Rice
K M
KM
Roch
M
M
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004032:Diet; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D012016:Reference Values
D018377:Neurotransmitter Agents; C038146:N-amino-N,N-dimethylaminoethanol; D002794:Choline