Effect of p-chlorophenylalanine on development of cross-tolerance between pentobarbital and ethanol

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Abstract
Rats developed cross-tolerance to the motor-impairing effects of ethanol after daily oral administration of pentobarbital. Chronic administration of p-chlorophenylalanine (p-CPA), in a dosage regimen previously demonstrated to maintain extensive brain serotonin (5-HT) depletion, slowed down cross-tolerance development. p-CPA did not appear to exert this effect by altering the disposition of ethanol, since blood ethanol levels measured 20 min after ethanol administration were not affected by p-CPA treatment. The inhibitory effects of p-CPA on tolerance development to ethanol and pentobarbital are discussed. 5-HT may play a role in cross-tolerance development between ethanol and pentobarbital.