A comparative study of the acute effects of ethanol on the cholinergic system in hippocampus and striatum of inbred mouse strains
Durkin, T.P.; Hashem-Zadeh, H.; Mandel, P.; Ebel, A.
Journal of Pharmacology and Experimental Therapeutics 220(1): 203-208
1982
ISSN/ISBN: 0022-3565 PMID: 7053416 Document Number: 189665
The acute effects of ethanol in vivo on the activity of choline acetyltransferase and the kinetics of choline uptake into crude synaptosomal (P2) fractions prepared from striatum and hippocampus were compared in the C57B1/6 and in the Balb/c mouse strains at various times (0-6 h) after the administration of ethanol by intragastric intubation. Acute treatment with 2-4.5 g/kg of ethanol produced a rapid inhibition of the Vmax of the Na-dependent high affinity choline uptake mechanism in striatum of C57B1/6, but not in Balb/c. In hippocampus a similar inhibition of high affinity choline uptake Vmax was observed for both strains. The inhibition of high affinity choline uptake in either brain region was rapid (almost maximal at 15 min post-treatment), dose-dependent and had a duration of 90-150 min. An inverse relation was observed for choline acetyltransferase activity because the inhibition of high affinity choline uptake was followed by an increase of this enzyme activity but with a longer latency and duration. No change in enzyme activity was obsered in Balb/c striatum. Ethanol in vivo produced no significant alteration to the KT of high affinity choline uptake nor to the kinetics of choline uptake by the Na-independent mechanism. Ethanol addition in vitro produced no changes to the kinetic constants of choline uptake by either mechanism in either mouse strain. These strain differences in the sensitivity of the central cholinergic system to ethanol are discussed in the context of the possible direct effects of ethanol on cholinergic neurons and also indirect effects via modifications to neurotransmitter interactions in these brain regions.