Changes in Ca2+ ion activity within unrestrained rat's hippocampus perfused with alcohol or acetaldehyde

In the freely moving rat, the kinetics of Ca2+ ion activity were determined at circumscribed sites in the hippocampus, which was perfused with ethanol, tertiary-butyl alcohol or acetaldehyde. Initially, a region in CA1 or other cell field of the dorsal hippocampus was prelabelled by microinjection of 45Ca2+ through a permanently implanted guide tube. Then the tip of a concentric push-pull cannula assembly was lowered through the guide tube to the labelled site, and an isotonic artificial cerebrospinal fluid was repeatedly perfused at a rate of 25 microliter/min. Each perfusion was timed for 5.0 min with a 5.0 min interval between each. Once the washout curve of 45Ca2+ activity had begun to approach its asymptote, ordinarily in the midpoint of a series of perfusions, an isotonic solution of ethanol (188-942 mM), tertiary-butyl alcohol (12-580 mM) or acetaldehyde (10-98 mM) was added to the fourth perfusate. Thereafter, the hippocampal site was again perfused with the normal cerebrospinal fluid for the remainder of the experiment. Although the lowest concentration of ethanol exerted no effect on 45Ca2+ ion activity, an intermediate concentration caused mixed effects in either enhancing or suppressing the efflux into the perfusate of this cation. The highest concentration of ethanol produced in most experiments an initial suppression in Ca2+ ion efflux which was followed frequently by an elevation in the release of 45Ca2+. Similar changes in Ca2+ ion activity were produced by tertiary-butyl alcohol, but the magnitude of its effect was generally less than that of ethanol, suggesting that its effect on brain tissue differs from that of ethanol. Acetaldehyde evoked an intense and concentration-dependent enhancement of Ca2+ ion efflux from the perfused tissue at all of the sites in the hippocampus examined. These results suggest that in the unrestrained rat ethanol could unbind Ca2+ ions from hippocampal membranes or retard their uptake into cells of the hippocampus. The dual excitatory and inhibitory effect of ethanol on Ca2+ ion activity corresponds to the electrophysiological effects of this alcohol and could alter neurotransmitter release from neurons in this subcortical structure. The mechanism of action of acetaldehyde is envisaged to be due to its affinity to membrane sulfhydryl groups which alters protein conformation and thus interferes with both Ca2+ channels and Ca2+ binding properties.