Log in

The modification of the ethanol withdrawal syndrome in rats by Di-n-propylacetate

  • Published:
Psychopharmacologia Aims and scope Submit manuscript

Abstract

Di-n-propylacetate (DPA), a drug known to increase brain γ-aminobutyric acid (GABA) levels and to inhibit GABA-transaminase (GABA-T) activity, was administered during the ethanol withdrawal period to rats made physically dependent upon ethanol. Under all conditions tested, 400 mg DPA/kg injected i.p. significantly reduced the withdrawal hyperexcitable state induced by acoustic stimulation. The effect was seen as early as 30 min after the administration of DPA and lasted for at least 2 hrs. Readministration of the same dose of DPA 6.5 hrs after its initial injection again mitigated withdrawal symptoms. A 200 mg/kg dose of DPA was significantly effective for only 1 hr after its administration. Neither dose led to mortality or observable tranquilization. The results suggest that DPA may be a useful agent in the control of the hyperexcitable state induced by ethanol withdrawal and that the GABA system may be involved in this state.

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

Access this article

Price includes VAT (Germany)

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Baxter, C. F., Roberts, E.: Elevation of γ-aminobutyric acid in brain: Selective inhibition of γ-aminobutyric-α-ketoglutaric acid transaminase. J. biol. Chem. 236, 3287–3294 (1961)

    Google Scholar 

  • Carraz, G.: In: Pharmacodynamie de l'acide dipropylacetique (ou propyl-2-pentanoique) et de ses amides. Grenoble: Imprimerie Eymond 1968

    Google Scholar 

  • Crossland, J., Turnbull, M. J.: Gamma-aminobutyric acid and the barbiturate abstinence syndrome in rats. Neuropharmacology 11, 733–738 (1972)

    Google Scholar 

  • Elliot, K. A. C., van Gelder, N. M.: The state of factor I in rat brain: The effects of metabolic conditions and drugs. J. Physiol. (Lond.) 153, 423–432 (1960)

    Google Scholar 

  • Essig, C. F.: Possible relation of brain gamma-aminobutyric acid (GABA) to barbiturate abstinence convulsions. Arch. int. Pharmacodyn. Ther. 176, 97–103 (1968)

    Google Scholar 

  • Freund, G.: Alcohol withdrawal syndrome in mice. Arch. Neurol. (Chic.) 21, 315–320 (1969)

    Google Scholar 

  • Freund, G.: The prevention of ethanol withdrawal seizures in mice by lidocaine. Neurology (Minneap.) 23, 92–94 (1973)

    Google Scholar 

  • Godin, Y., Heiner, L., Mark, J., Mandel, P.: Effects of di-n-propylacetate, an anticonvulsive compounds, on GABA metabolism. J. Neurochem. 16, 869–873 (1969)

    Google Scholar 

  • Goldstein, D. B.: Alcohol withdrawal reactions in mice: Effects of drugs that modify neurotransmission. J. Pharmacol. exp. Ther. 186, 1–9 (1973)

    Google Scholar 

  • Goldstein, D., Pal, N.: Alcohol dependence produced in mice by inhalation of ethanol: Grading the withdrawal reaction. Science 172, 288–290 (1971)

    Google Scholar 

  • Jeavons, P. N., Clark, J. E.: Sodium valproate in treatment of epilepsy. Brit. med. J. 1974II, 584–586

    Google Scholar 

  • Killam, K. F., Bain, J. A.: Convulsant hydrazides I: In vitro and in vivo inhibition of vitamin B6 enzymes by convulsant hydrazides. J. Pharmacol. exp. Ther. 119, 255–262 (1957)

    Google Scholar 

  • Kuriyama, K., Roberts, E., Rubenstein, M. K.: Elevation of gamma-aminobutyric acid in brain with amino-oxyacetic acid and susceptibility to convulsive seizures in mice: A quantitative re-evaluation. Biochem. Pharmacol. 15, 221–236 (1966)

    Google Scholar 

  • Leberton, S., Carraz, G., Meunier, H., Beriel, H.: Propriétés pharmacodynamiques de l'acide N-dipropylacétique. Deuxième mémoire sur les propriétés antileptiques. Thérapie 19, 451–476 (1964)

    Google Scholar 

  • Lieber, C. S., DeCarli, L. M.: Ethanol dependence and tolerance: A nutritionally controlled experimental model in the rat. Res. Commun. Chem. Path. Pharmacol. 6, 983–991 (1973)

    Google Scholar 

  • Maitre, L., Ciesielski, L., Mandel, P.: Effect of 2-methyl 2-ethyl caproic acid and 2-2-dimethyl valeric acid on audiogenic seizures and gamma aminobutyric acid. Biochem. Pharmacol. 23, 2363–2368 (1974)

    Google Scholar 

  • Majchrowicz, E.: Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia (Berl.) 43, 245–254 (1975)

    Google Scholar 

  • Meunier, H., Carraz, G., Meunier, Y., Eymard, P., Airmard, M.: Propriétés pharmacodynamique de l'acide n-dipropylacétique. Thérapie 18, 435–438 (1963)

    Google Scholar 

  • Noble, E. P., Tewari, S.: Metabolic aspects of alcoholism in the brain. In: Metabolic aspects of alcoholism, C. S. Lieber, ed. Lancaster, England: Medical and Technical Publishing Co., Ltd. (in press, 1975)

  • Purpura, D. P., Girado, M., Smith, T. G., Gomez, J. A.: Synaptic effects of systemic γ-amino butyric acid in cortical regions of increased vascular permeability. Proc. Soc. exp. Biol. (N. Y.) 97, 348–353 (1958)

    Google Scholar 

  • Roberts, E., Kuriyama, K.: Biochemical-physiological correlations in studies of the γ-aminobutyric acid system. Brain Res. 8, 1–35 (1968)

    Google Scholar 

  • Siegel, S.: Nonparametric statistics for the behavioral sciences. New York: McGraw-Hill 1956

    Google Scholar 

  • Simler, S., Ciesielski, L., Maitre, M., Randrianarisoa, H., Mandel, P.: Effect of sodium n-dipropylacetate on audio-genic seizures and brain γ-aminobutyric acid level. Biochem. Pharmacol. 22, 1701–1708 (1973)

    Google Scholar 

  • Simler, S., Randrianarisoa, H., Lehmann, A., Mandel, P.: Effects du di-n-propylacétate sur les crises audiogènes de la souris. J. Physiol. (Paris) 60 (Suppl. 2), 547 (1968)

    Google Scholar 

  • Simler, S., Randrianarisoa, H., Lehmann, A., Mandel, P.: In: Pathogenesis of epilepsy. G. Usunoff, E. Atsev, I. Dosseva, and S. Dimov, eds., pp. 59–70. Sofia: Publishing House of the Bulgarian Academy of Sciences 1971

    Google Scholar 

  • Völzke, E., Doose, H.: Epilepsia. J. Internat. League against Epilepsy 14, 185 (1973)

    Google Scholar 

  • Wallgren, H., Kosunen, A.-L., Ahtee, L.: Technique for producing an alcohol withdrawal syndrome in rats. Israel J. med. Sci. 9 (Suppl.), 63–71 (1973)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Noble, E.P., Gillies, R., Vigran, R. et al. The modification of the ethanol withdrawal syndrome in rats by Di-n-propylacetate. Psychopharmacologia 46, 127–131 (1976). https://doi.org/10.1007/BF00421381

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00421381

Key words

Navigation