Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Acute tolerance to ethanol using drug discrimination and open-field procedures in rats


This study examined the phenomenon of acute tolerance to ethanol (ETOH) using drug discrimination learning (DDL), and open-field (OF) procedures. In DDL, rats were trained to discriminate between ETOH (1.2 g/kg) and saline. Doses of ETOH lower (0.6 and 0.9 g/kg), or higher (1.8 and 2.4 g/kg) than the training dose were tested to examine possible influence of ETOH pretreatment doses on the expression of acute tolerance. To assess concentrations of ETOH in the organism, a rebreathed air procedure was used. Equal concentrations after different ETOH doses were achieved by postponing the tests until sufficient time had elapsed. Only doses of ETOH higher than the training dose produced acute tolerance in the DDL procedure. For the response-time data no acute tolerance was observed. In the OF experiment, the occurrence of acute tolerance was examined for different spontaneous behaviours in drug-naive animals. At equal ETOH concentrations, the group examined during the descending phase of intoxication (1.8 g/kg, 60 min post-injection), reared significantly more than the group tested during the ascending phase (1.5 g/kg, 10 min post-injection). Other OF behaviours did not differ significantly between the two time intervals. Thus, it is suggested that acute tolerance is seen both in ETOH naive and in ETOH pre-exposed rats. However, in DDL acute tolerance was observed only when doses higher than the training dose of ETOH were evaluated.

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


  1. Campanelli C, Lê AD, Khanna JM, Kalant H (1988) Effect of raphe lesions on the development of acute tolerance to ethanol and pentobarbital. Psychopharmacology 96:454–457

  2. Caul WF, Burgin KL, Barrett RJ (1989) Drug discrimination training during chronic drug treatment affects the development of tolerance. Behav Neurosci 103:373–377

  3. Chait LD, Uhlenhuth EH, Johanson CE (1985) The discriminative stimulus and subjective effects ofd-amphetamine in humans. Psychopharmacology 86:307–312

  4. Chait LU, Uhlenhuth EH, Johanson CE (1986a) The discriminative stimulus and subjective effects ofd-amphetamine, phenmetrazine and fentheramine in humans. Psychopharmacology 89:301–306

  5. Chait LD, Uhlenhuth EH, Johanson CE (1986b) The discriminative stimulus and subjective effects of phenylpropanolamine, mazindol andd-amphetamine in humans. Pharmacol Biochem Behav 24:1665–1672

  6. Colpaert FC (1978) Narcotic cue, narcotic analgesia, and the tolerance problem: the regulation of sensitivity to drug cues and to pain by an internal cue processing model. In: Colpaert FC, Rosecrans JA (eds) Stimulus properties of drugs: ten years of progress. Elsevier/North Holland Biomedical Press, Amsterdam, pp 301–321

  7. Ekman G, Frankenhauser M, Goldberg L, Hagdahl R, Myrsten AL (1964) Subjective and objective effects of alcohol as functions of dosage and time. Psychopharmacologia 6:399–409

  8. Ellinwood EH, Linnoila M, Easler ME, Molter DW (1983) Profile of acute tolerance to three sedative anxiolytics. Psychopharmacology 79:137–141

  9. Emmett-Oglesby MW, Spencer DG Jr, Arnoult DE (1982) A TRS-80-based system for the control of behavioral experiments. Pharmacol Biochem Behav 17:583–587

  10. Extance K, Goudie AJ (1981) Inter-animal olfactory cues in drug discrimination procedures in rats. Psychopharmacology 73:363–371

  11. Franks HM, Starmer GA, Teo RKC (1974) Acute adaptation of human cognitive and motor functions to ethanol. Proc 7th Int Conf Alc Drugs and Traffic Safety, pp 190–199

  12. Goldberg L (1943) Quantitative studies on alcohol tolerance in man. The influence of ethyl alcohol on memory, motor and psychological functions referred to blood alcohol in normal and habituated individuals. Acta Physiol Scand [Suppl] 16:5–42

  13. Gostomzyk JG, Streffer C (1969) Tierexperimentelle Untersuchungen zur Verteilung von Äthylalkohol in verschiedenen Organen, insbesondere im Gehirn, während der Resorptionsphase. Blutalkohol 6:211–224

  14. Gostomzyk JG, Dilger B, Dilger K (1969) Untersuchungen über die arteriovenöse Differenz der Alkoholkonzentration im Blut and ihre Beziehung zum Alkoholgehalt des Gehirns. Z Klin Chem und Klin Biochem 7:162–166

  15. Haubenreisser T, Vogel-Sprott M (1987) Reinforcement reduces behavioral impairment under an acute dose of alcohol. Pharmacol Biochem Behav 26:29–33

  16. Hiltunen AJ, Järbe TUC (1986) Interactions between Δ9-tetrahydrocannabinol and cannabidiol as evaluated by drug discrimination procedures in rats and pigeons. Neuropharmacology 25:133–142

  17. Hiltunen AJ, Järbe TUC, Wängdahl K (1988) Cannabinol and cannabidiol in combination: temperature, open-field activity, and vocalization. Pharmacol Biochem Behav 30:675–678

  18. Hiltunen AJ, Järbe TUC, Hellström-Lindahl E, Croon L-B, Jones AW (1989) Concentrations of ethanol in rebreathed air of rats: correlation with the discriminative stimulus effects of ethanol. Alcohol 6:39–43

  19. Järbe TUC, Hiltunen AJ (1987) Cannabimimetic activity of cannabinol in rats and pigeons. Neuropharmacology 26:219–228

  20. Johanson CE, Fischman MW (1989) The pharmacology of cocaine related to its abuse. Pharmacol Rev 41:3–52

  21. Jones AW (1978) Variability of the blood: breath alcohol ratio in vivo. J Stud Alcohol 39:1931–1939

  22. Kaplan HL, Sellers EM, Hamilton C, Naranjo CA, Dorian P (1985) Is there acute tolerance to alcohol at steady state. J Stud Alcohol 46:253–256

  23. Kirk RE (1968) Experimental design: procedures for the behavioral sciences. Brooks/Cole, California

  24. LeBlanc AE, Kalant H, Gibbins RJ (1975) Acute tolerance to ethanol in the rat. Psychopharmacologia 41:43–46

  25. Linakis JG, Cunningham CL (1979) Effects of concentration of ethanol injected intraperitoneally on taste aversion, body temperature, and activity. Psychopharmacology 64:61–65

  26. Martin E, Moll W, Schmid P, Dettli L (1984) The pharmacokinetics of alcohol in human breath, venous and arterial blood after oral ingestion. Eur J Clin Pharmacol 26:619–626

  27. Mellanby E (1919) Alcohol: its absorbtion into and disappearance from the blood under different conditions. G B Med Res Council Spec Rep Ser 31:1–48

  28. Moskowitz H, Daily J, Henderson R (1979) The Mellanby effect in moderate and heavy drinkers. Proc 7th Int Conf Alc Drugs and Traffic Safety, pp 184–189

  29. Pohorecky LA, Brick J (1982) A new method for the determination of blood ethanol levels in rodents. Pharmacol Biochem Behav 16:693–696

  30. Portans I, White JM, Staiger PK (1989) Acute tolerance to alcohol: changes in subjective effects among social drinkers. Psychopharmacology 97:365–369

  31. Radlow R, Hurst PM (1985) Temporal relations between blood alcohol concentration and alcohol effect: an experiment with human subjects. Psychopharmacology 85:260–266

  32. Spencer DG Jr, Emmett-Oglesby MW (1985) Parallel processing strategies in the application of microcomputers to the behavioral laboratory. Behav Res Meth Instrum 17:294–300

  33. Sunahara GI, Kalant H, Schofield M, Grupp I (1978) Regional distribution of ethanol in the rat brain. Can J Physiol Pharmacol 56:988–992

  34. Tullis KV, Sargent WQ, Simpson JR, Beard JD (1977) An animal model for the measurement of acute tolerance to ethanol. Life Sci 20:875–882

  35. Vogel-Sprott MD (1979) Acute recovery and tolerance to low doses of alcohol: differences in cognitive and motor skill performance. Psychopharmacology 61:287–291

  36. Wahlström G, Widerlöv E (1971) Interaction and acute tolerance between ethanol and hexobarbitone in the rat. J Pharm Pharmacol 23:58–60

  37. Witkin JM, Dykstra LA, Carter RB (1982) Acute tolerance to the discriminative stimulus properties of morphine. Pharmacol Biochem Behav 17:223–228

  38. Wood DM, Emmett-Oglesby MW (1986) Characteristics of tolerance, recovery from tolerance and cross-tolerance for cocaine used as a discriminative stimulus. J Pharmacol Exp Ther 237:120–125

  39. Wood DM, Lal H, Emmett-Oglesby M (1984) Acquisition and recovery of tolerance to the discriminative stimulus properties of cocaine. Neuropharmacology 23:1419–1423

Download references

Author information

Correspondence to Arto J. Hiltunen.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hiltunen, A.J., Järbe, T.U.C. Acute tolerance to ethanol using drug discrimination and open-field procedures in rats. Psychopharmacology 102, 207–212 (1990). https://doi.org/10.1007/BF02245923

Download citation

Key words

  • Acute tolerance
  • ETOH
  • Drug discrimination
  • Open-field
  • Rats