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Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats. Bartus RT, Dean RL 3rd, Sherman KA, Friedman E, Beer B. Neurobiol Aging. 1981 Summer;2(2):105-11Abstract In an attempt to gain some insight
into possible approaches to reducing age-related memory
disturbances, aged Fischer 344 rats were administered either
vehicle, choline, piracetam or a combination of choline or
piracetam. Animals in each group were tested behaviorally for
retention of a one trial passive avoidance task, and biochemically
to determine changes in choline and acetylcholine levels in
hippocampus, cortex and striatum. Previous research has shown that
rats of this strain suffer severe age-related deficits on this
passive avoidance task and that memory disturbances are at least
partially responsible. Those subjects given only choline (100 mg/kg)
did not differ on the behavioral task from control animals
administered vehicle. Rats given piracetam (100 mg/kg) performed
slightly better than control rats (p less than 0.05), but rats given
the piracetam/choline combination (100 mg/kg of each) exhibited
retention scores several times better than those given piracetam
alone. In a second study, it was shown that twice the dose of
piracetam (200 mg/kg) or choline (200 mg/kg) alone, still did not
enhance retention nearly as well as when piracetam and choline (100
mg/kg of each) were administered together. Further, repeated
administration (1 week) of the piracetam/choline combination was
superior to acute injections. Regional determinations of choline and
acetylcholine revealed interesting differences between treatments
and brain area. Although choline administration raised choline
content about 50% in striatum and cortex, changes in acetylcholine
levels were much more subtle (only 6-10%). No significant changes
following choline administration were observed in the hippocampus.
However, piracetam alone markedly increased choline content in
hippocampus (88%) and tended to decrease acetylcholine levels (19%).
No measurable changes in striatum or cortex were observed following
piracetam administration. The combination of choline and piracetam
did not potentiate the effects seen with either drug alone, and in
certain cases the effects were much less pronounced under the drug
combination. These data are discussed as they relate to possible
effects of choline and piracetam on cholinergic transmission and
other neuronal function, and how these effects may reduce specific
memory disturbances in aged subjects. The results of these studies
demonstrate that the effects of combining choline and piracetam are
quite different than those obtained with either drug alone and
support the notion that in order to achieve substantial efficacy in
aged subjects it may be necessary to reduce multiple, interactive
neurochemical dysfunctions in the brain, or affect activity in more
than one parameter of a deficient metabolic pathway.
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