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Journal of Pharmacology and Experimental Therapeutics

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OtherNEUROPHARMACOLOGY

Acetylcholine Release and Choline Availability in Rat Hippocampus: Effects of Exogenous Choline and Nicotinamide

Andrea Köppen, Jochen Klein, Christina Erb and Konrad Löffelholz
Journal of Pharmacology and Experimental Therapeutics September 1997, 282 (3) 1139-1145;
Andrea Köppen
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Jochen Klein
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Christina Erb
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Konrad Löffelholz
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Abstract

The influence of choline availability on acetylcholine (ACh) release in the hippocampus of the awake rat was investigated using the microdialysis procedure. Three treatments enhancing choline availability for basal and atropine-evoked ACh release were evaluated: acute administration of choline chloride (20 mg/kg i.p.); pretreatment of animals with nicotinamide (10 mmol/kg s.c.) 2 hr before atropine injection and dietary choline supplementation (5-fold increase of choline intake for 15–18 days). Although acute choline administration led to a short-lasting (15 min) increase of basal choline efflux by 25% and nicotinamide caused a long-lasting (5 hr) increase by 105%, neither one affected basal ACh release. However, basal release of choline (1.38 pmol/min) and of ACh (114 fmol/min) in the hippocampus was slightly increased in choline-supplemented animals (choline: 1.92 pmol/min; ACh: 140 fmol/min). In untreated animals, atropine administration caused a 3-fold increase of ACh efflux that lasted approximately 2.5 hr. All treatments, acute or chronic choline and nicotinamide, led to significant increases of the maximum and duration of atropine-evoked ACh release. Total atropine-evoked ACh efflux (area under the curve) was increased 2- to 3-fold, with the largest effect evoked by the combination of nicotinamide and choline. The results clearly demonstrate that, under stimulated conditions, hippocampal ACh release could be facilitated when the availability of choline for ACh synthesis was enhanced by dietary or pharmacological means. Under certain conditions, significant effects of increased choline availability on ACh release can be revealed in the absence of an overall increase of extracellular choline.

Footnotes

  • Send reprint requests to: Dr. Jochen Klein, Department of Pharmacology, University of Mainz, Obere Zahlbacher Str. 67, D-55101 Mainz, Germany.

  • ↵1 This study was supported by the Deutsche Forschungsgemeinschaft.

  • Abbreviations:
    ACh
    acetylcholine
    AUC
    area under the concentration vs. time curve
    CNS
    central nervous system
    CSF
    cerebrospinal fluid
    HACU
    high affinity choline uptake
    HPLC
    high-pressure liquid chromatography
    • Received September 18, 1996.
    • Accepted April 7, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 3
1 Sep 1997
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OtherNEUROPHARMACOLOGY

Acetylcholine Release and Choline Availability in Rat Hippocampus: Effects of Exogenous Choline and Nicotinamide

Andrea Köppen, Jochen Klein, Christina Erb and Konrad Löffelholz
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1139-1145;

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OtherNEUROPHARMACOLOGY

Acetylcholine Release and Choline Availability in Rat Hippocampus: Effects of Exogenous Choline and Nicotinamide

Andrea Köppen, Jochen Klein, Christina Erb and Konrad Löffelholz
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1139-1145;
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