Tolerance, physical dependence and changes in muscarinic receptor binding sites after chronic ethanol treatment in the rat.

Rats were treated with ethanol in the drinking water for 73-75 weeks. The daily drinking periods were restricted to only 2x1 h to get significant ethanol blood concentrations. After the end of the ethanol treatment (last day of treatment denoted day 0 of the abstinence) tolerance to sedatives were recorded with a hexobarbital threshold method, convulsions recorded with jiggle cages, and muscarinic receptor binding sites determined with 3H-quinuclidinyl benzilate. Tolerance to hexobarbital was found to have a maximum on day 8 in the abstinence while convulsions recorded from the rats participating in the hexobarbital threshold determinations had a maximum on day 14. Atropine administered as a single dose on day 8 decreased the tolerance to hexobarbital on that day and seemed to reduce the number of convulsions on the following days. Muscarinic receptor sites were significantly increased in the striatum on day 8 of the abstinence at the time of maximal tolerance, This increase in muscarinic receptors was less in rats which had had convulsions during the abstinence before sacrifice. Thus the results indicate that cholinergic mechanisms are involved in the changes seen during the abstinence after chronic ethanol exposure.