Global in vivo replacement of choline by N-aminodeanol. Testing a hypothesis about progressive degenerative dementia: II. Physiological and behavioral effects.
We have examined the progressive effects of replacement of dietary choline with NADe for a period of 120 days on a broad spectrum of behavioral and physiological functions known to involve the cholinergic system. The magnitudes of these effects tended to increase with time on the NADe diet, but those related to learning and memory were largely confined to the 60-120-day period. Neurochemical effects were concomitant with the replacement of Ch by NADe, being consistent with a hypocholinergic state as found in such progressive degenerative dementias as Alzheimer's disease. As cholinergic functioning was progressively impaired, basic physiological ("vegetative") processes appeared not to be affected. Apparently the rate at which the hypofunctional state developed was sufficiently slow for adjustments to occur, allowing the animal to adapt at a survival level to neurochemical changes. More complex behavioral functions were affected progressively, cognitive processes (e.g., learning and memory) being most sensitive and showing the least adaptability. We propose that the syndrome generated by NADe replacement of Ch represents an experimental model of progressive degenerative dementia.
Russell
R W
RW
Department of Pharmacology, School of Medicine, University of California, Los Angeles 90024.
Jenden
D J
DJ
Booth
R A
RA
Lauretz
S D
SD
Rice
K M
KM
Roch
M
M
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D004032:Diet; D004327:Drinking Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D006128:Growth / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects; D011247:Pregnancy; D051381:Rats
D018377:Neurotransmitter Agents; C038146:N-amino-N,N-dimethylaminoethanol; D002794:Choline