The interaction between electrically induced convulsions and tolerance in the abstinence period after chronic barbital treatments in the rat.

The effect of electrically induced convulsions was tested on the tolerance to hexobarbital after chronic barbital treatment in male rats. In two experiments barbital was given in the drinking water for more than 20 weeks. The dose was around 200 mg/kg/day. Tolerance was tested with an EEG threshold method where hexobarbital is infused intravenously to obtain a criterion of burst suppression. If on the third abstinent day an electrical convulsion was induced 1 h prior to the threshold determination then the hexobarbital thresholds were reduced compared with barbital-treated animals where no convulsion had been induced (Fig.2). The distribution of hexobarbital threshold doses tended to be biphasic in the barbital-treated animals where a convulsion had been induced. The animals with the most "normal" thresholds in this distribution did not show any increase in threshold on the 24th abstinent day and had a larger mortality during the observation period after the first barbital treatment. Long-term effects of the convulsion thus cannot be excluded in rats if the tolerance on the third abstinent day after a barbital treatment was influenced. No effect of the convulsion was found in untreated controls. The hypothesis that convulsions are means to reduce the changes of physical dependence in the central nervous system was not refuted by the present experiments. A survey of the literature indicates that acetylcholine might be one central nervous transmittor that is involved in these changes.