Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Altered sensitivity to ethanol following prenatal exposure to barbiturate

  • 10 Accesses

  • 14 Citations


Female mice (genetically heterogeneous stock) were fed milled mouse food containing 3 g/kg phenobarbital (PhB) and water as their only nutritional source from gestation days 9–18. Control dams received milled food and water. Blood PhB levels of treated females and fetuses were 40–200 μg/ml. At the age of 50 days, male offspring were injected with 3.5 g/kg ethanol. Sleep time was monitored and in randomly selected individuals, brain ethanol levels were determined upon awakening. To assess the rate of metabolism in the treated and control offspring, blood ethanol levels were determined in other randomly selected individuals at 60 and 120 min post-injection. Offspring who received PhB prenatally were resistant to the hypnotic effects of ethanol as evidenced by their 33% shorter sleep time compared to controls (P<0.001). The brain ethanol levels upon awakening were higher than control in the offspring born to the barbiturate-treated mothers (P<0.001), indicating that the resistance to ethanol was due to factors residing within the central nervous system.

This is a preview of subscription content, log in to check access.


  1. Frankel, D., Khanna, J. M., LeBlanc, A. E., Kalant, H.: Effect of p-chlorophenylalanine on development of cross-tolerance between pentobarbital and ethanol. Can. J. Physiol. Pharmacol. 55, 954–957 (1977)

  2. Frankel, D., Khanna, J. M., Kalant, H., LeBlanc, A. E.: Effect of p-chlorophenylalanine on the loss and maintenance of tolerance to ethanol. Psychopharmacology 56, 139–143 (1978)

  3. Fraser, H. F., Wikler, A., Isbell, H., Johnson, H. K.: Partial equivalence of chronic alcohol and barbiturate intoxications. Q. J. Stud. Alcohol 18,541–551 (1957)

  4. Hill, R. M.: Drugs ingested by pregnant women. Clin. Pharmacol. Ther. 14, 654–659 (1973)

  5. Kalant, H., LeBlanc, A. E., Gibbons, R. J.: Tolerance to, and dependence on, some non-opiate psychotropic drugs. Pharmacol. Rev. 23, 135–180 (1971)

  6. Kalant, H., Khanna, J. M., Marshman, J.: Effect of chronic intake of ethanol on pentobarbital metabolism. J. Pharmacol. Exp. Ther. 175, 318–324 (1970)

  7. Ornoy, A., Yanai, J.: Central nervous system teratogenicity; Experimental models for human problems. In: Advances in the study of birth defects, Vol. 4. Neural and behavioral teratology. T. V. N. Persaud, ed., pp.1–21. Lancaster, England: MTP Press 1980

  8. Soehring, K., Schuppel, R.: Wechselwirkungen zwischen Alkohol and Arzneimitteln. Dtsch. Med. Wochenschr. 91, 1892–1896 (1966)

  9. Speroff, L.: Toxemia of pregnancy: Mechanism and therapeutic management. Am. J. Cardiol. 32, 582–591 (1973)

  10. Stiles, D., Batsakis, J., Kremers, B., Briere, A.: The evaluation of ethanol measurement with alcohol dehydrogenase. Am. J. Clin. Pathol. 46, 608–611 (1966)

  11. Tabakoff, B., Yanai, J.: Cortexolone antagonizes development of alcohol tolerance in mice. Psychopharmacology 6, 123–124 (1979)

  12. Tabakoff, B., Ritzmann, R. F., Hoffman, P. L.: Role of catecholamines in the development of tolerance to barbiturates and ethanol. In. In: Advances in experimental medicine vol. 85A, M. M. Cross, ed., pp. 155–168. New York: Plenum 1977

  13. Thomas, C. R.: Routine phenobarbital for prevention of neonatal hyperbilirubinemia. Obstet. Gynecol. 47, 304–308 (1976)

  14. Trolle, D.: Phenobarbitone and neonatal icteruf. Lancet 1968I, 251–252

  15. Wahlstrom, G.: Changes in a hexobarbital anesthesia threshold in rats induced by repeated long-term treatment with barbital or ethanol. Psychopharmacologia 19, 366–380 (1971)

  16. Winer, B. J.: Statistical principles in experimental design. New York: McGraw Hill 1971

  17. Yanai, J.: Long-term induction of microsomal drug oxidizing system in mice following prenatal exposure to barbiturate. Biochem. Pharmacol. 28, 1429–1430 (1979)

  18. Yanai, J., Tabakoff, B.: Increased tolerance in mice following prenatal exposure to barbiturate. Psychopharmacology 64, 325–327 (1979)

  19. Yanai, J., Rosselli-Austin, L., Tabakoff, B.: Neuronal deficits in mice following prenatal exposure to phenobarbital. Exp. Neurol. 64, 237–244 (1979)

Download references

Author information

Correspondence to Joseph Yanai.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yanai, J., Tabakoff, B. Altered sensitivity to ethanol following prenatal exposure to barbiturate. Psychopharmacology 68, 301–303 (1980).

Download citation

Key words

  • Barbiturate
  • Blood ethanol level
  • Brain ethanol level
  • Ethanol sensitivity
  • Ethanol
  • Ethanol metabolism
  • Mice
  • Prenatal exposure
  • Sleep time