Comparison of ethanol and barbiturate physical dependence.

The physical dependence and tolerance characteristics of barbiturates and ethanol were compared. One group of cats was given anesthetic doses of pentobarbital chronically to produce severe physical dependence ("high dose" group). Two other groups of animals were given barbital or ethanol at "chronically equivalent" doses which produced gross ataxia without anesthesia ("low dose" groups). The doses required to produce the preset level of central nervous system depression progressively increased in all three groups during the chronic administration. Functional tolerance estimated by measuring the drug concentration in the blood at the peak of the drug response was demonstrated in all three groups. Drug administration was terminated after various durations and withdrawal was rated. Severity of withdrawal was assessed by monitoring spontaneous convulsions and by rating motor, autonomic and behavioral signs. These ratings were used to compute peak intensity of withdrawal. The number of convulsions, incidence of lethality during withdrawal and peak withdrawal intensity ratings were considerably higher in the ethanol groups than in the low dose barbiturate groups. Similarly, the number of convulsions, incidence of lethality during withdrawal and peak intensity ratings were consistently higher in the high dose barbiturate groups than in the low dose barbiturate groups. The results indicate that ethanol produced more severe withdrawal than barbiturate when the level of chronic intoxication was comparable in the two groups. Also, the level of central nervous system depression during administration was an important factor influencing intensity of barbiturate withdrawal.