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High-Affinity Choline Uptake in the Hippocampus: Its Relationship to the Physiological State Produced by Administration of Barbiturates and Other Treatments
Authors:Judith A. Richter&dagger  ,Joanne M. Gormley,Joseph R. Holtman,Jr., Jay R. Simon&dagger  &dagger  
Affiliation:Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.;Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.;Department of Biochemistry, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
Abstract:Abstract: Choline uptake in hippocampal synaptosomes was not inhibited by pentobarbital administration when rats were decapitated immediately upon loss of the righting reflex (3–4 min) even though it was inhibited at later times post-injection, when the rats were still unable to right themselves. Choline uptake was increased when the animals were decapitated at convulsion after an injection of picrotoxin, high doses of bicuculline, or one of the convulsant barbiturates. However, another convulsant barbiturate, as well as strychnine and lower doses of bicuculline, did not increase choline uptake even though the animals also convulsed. Thus loss of righting reflex or convulsion is not directly correlated with changes in choline uptake. At 7 min after injection, levels of pentobarbital in the hippocampus (and other brain regions) were correlated with the degree of inhibition of choline uptake up to about 50% inhibition; however, greater inhibition could not be achieved with much higher brain levels of the drug. Although hippocampal uptake was partially inhibited at 1 h after septal lesions, 3 h after the lesion the inhibition was no longer apparent. Inhibition was almost complete 10–12 days after the lesion. These results suggest that other factors in addition to impulse flow influence choline uptake.
Keywords:High-affinity choline uptake    Barbiturates    Hippocampus    Synaptosomes    Cholinergic system    Convulsants
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