Advertisement

Acute and Chronic Effects of Barbiturates on Regional Turnover of Acetylcholine in Brain

  • Agneta Nordberg
  • Göran Wahlström
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 126)

Summary

Data concerning both the acute and chronic effects of barbiturates on acetylcholine [ACh] turnover in mouse and rat brain are presented

A single anaesthetic dose of pentobarbital [60 mg/kg, i.p.] to mice increased the endogenous content of ACh and decreased the turnover of ACh in the hippocampus and cortex. No effect was found in the striatum

At sacrifice after chronic treatment with barbital to rats for about 30 weeks no effect was found on the endogenous ACh content. 3 days after the barbital solution was replaced by water [at the day with maximal number of abstinence convulsions] the amount of endogenous ACh was decreased by 35% in the striatum in comparison with control and the decrease was still significant after 30 days of abstinence

The biosynthesis of radioactive ACh from a tracer dose of radioactive choline [Ch] was increased in the cerebellum+midbrain+medulla oblongata of rats receiving barbital until sacrifice and rats abstinent for 3 days. It was also increased in the hippocampus+cortex on the 3rd abstinent day. No significant effect on the ACh formation was found in the striatum

Keywords

Microwave Irradiation Medulla Oblongata speciFic Radioactivity Tracer Dose Acta Physiol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aquilonius, S.-M., Eckernäs, S.A., and Sundwall, Å. Regional distribution of choline acetyltransferase in the human brain: changes in Huntington’s chorea. J. Neurol. Neurosurg. Psychiat., 1975, 38: 669–677PubMedCrossRefGoogle Scholar
  2. Atweh, S., Simon, J.R., and Kuhar, M.J. Utilization of sodium — dependent high affinity choline uptake in vitro as a measure of the activity of cholinergic neurons in vivo. Life Sci., 1975, 17: 1535–1544PubMedCrossRefGoogle Scholar
  3. Elliot, K.A.C., Swank, R.L., and Henderson, N. Effects of anaesthetics and convulsants on acetylcholine content of brain. Amer. J. Physiol., 1950, 162: 469–474Google Scholar
  4. Ellman, G.L., Courtney, K.D., Andres, V., and Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7: 88–95PubMedCrossRefGoogle Scholar
  5. Giarman, N. J. and Pepeu, G. Drug-induced changes in brain acetylcholine. Brit. J. Pharmacol., 1962, 19: 226–234PubMedGoogle Scholar
  6. Glowinski, J., and Iversen, L. L. Regional studies of catecholamines in the rat brain-I. J. Neurochem., 1966, 13: 655–669PubMedCrossRefGoogle Scholar
  7. McBride, A., and Turnbull, M.J. The brain acetylcholine in barbitone dependent and withdrawn rats. Brit. J. Pharmacol., 1970, 39: 210–211Google Scholar
  8. Modak, A.T., Weintraub, S.T., McCoy, T.H., and Stavinoha, W.B. Use of 300-msec microwave irradiation for enzyme inactiviation: a study of effects of sodium pentobarbital on acetylcholine concentration in mouse brain regions. J. Pharmacol. Exp. Ther., 1976, 197: 245–252PubMedGoogle Scholar
  9. Nordberg, A. Apparent regional turnover of acetylcholine in mouse brain — Methodological and functional aspects. Acta physiol. scand. suppl., 1977, 445: 1–51PubMedGoogle Scholar
  10. Nordberg, A. Regional high affinity synaptosomal transport: of choline in mouse brain — influence of oxotremorine treatment. Life Sci., 1978, 23: 937–944PubMedCrossRefGoogle Scholar
  11. Nordberg, A., and Sundwall, A. Effect of pentobarbital on endogenous acetylcholine and biotransformation of radioactive choline in different brain regions. In P. G. Waser [Ed.] Cholinergic Mechanisms. New York, Raven Press, 1975. 229–239Google Scholar
  12. Nordberg, A., and Sundwall, A. Biosynthesis of acetylcholine in different brain regions in vivo following alternative methods of sacrifice by microwave irradiation. Acta physiol. scand., 1976, 98: 307–317PubMedCrossRefGoogle Scholar
  13. Nordberg, A., and Sundwall, A. Effect of sodium pentobarbital on the apparent turnover of acetylcholine in different brain regions. Acta physiol. scand., 1977, 99: 336–344PubMedCrossRefGoogle Scholar
  14. Nordberg, A., and Wahlström, G. Effect of long-term forced oral barbital administration on endogenous acetylcholine in different regions of rat brain. Eur. J. Pharmacol., 1977, 43: 237–242PubMedCrossRefGoogle Scholar
  15. Nordberg, A., and Wahlström, G. Regional biosynthesis of acetylcholine in brain following forced oral chronic barbitone treatment to rat. J. Neurochem., 1978, in pressGoogle Scholar
  16. Richter, D., and Crossland, J. Variation in acetylcholine content of the brain with physiological state. Amer. J. Physiol., 1949, 159: 247–255PubMedGoogle Scholar
  17. Schuberth, J., Sparf, B., and Sundwall, A. A technique for the study of acetylcholine turnover in mouse brain in vivo. J. Neurochem., 1969, 16: 695–700PubMedCrossRefGoogle Scholar
  18. Tobias, J.M., Lipton, M.A., and Lepinat, A.A. Effect of anesthetics and convulsants on brain acetylcholine content. Proc. See. exp. Biol. N.Y., 1946, 61: 51–54CrossRefGoogle Scholar
  19. Trabucchi, M., Cheney, D.L., Racagni, G., and Costa, E. Pentobarbital and in vivo turnover rate of acetylcholine in mouse brain and in regions of rat brain. Pharmacol. Res. Commun., 1975, 7: 81–94CrossRefGoogle Scholar
  20. Wahlström, G. Hexobarbital [Enhexymalum NFN] sleeping times and EEG threshold doses as measurements of tolerance to barbiturates in the rat. Acta Pharmacol. Toxicol., 1968, 26: 64–80CrossRefGoogle Scholar
  21. Wahlström, G. Withdrawal in the rat after long-term forced oral barbital administration. Acta Pharmacol. Toxicol., 1974, 35: 131–144CrossRefGoogle Scholar
  22. Wahlström, G. The irrteraction between spon-taneous convulsions and tolerance to hexobarbital in the abstinence after chronic barbital treatment in the rat. Life Sci., 1976, 19: 1817–1826PubMedCrossRefGoogle Scholar
  23. Wahlström, G. Addictive drugs and some neurotransmitters [Acetylcholine and gamma-aminobutyric acid]. In J. Fisherman [Ed.] The basis of addiction. Berlin, Dahlem Konferenzen, 1978a. 353–374Google Scholar
  24. Wahlström, G. Some aspects on the changes induced by chronic barbital treatment in the male rat. In B. Tabakoff [Ed.] Theories of tolerance and dependence on ethanol: Mechanistic approaches. Elsevier Sequoia, S.A., 1978b, in pressGoogle Scholar
  25. Wahlström, G. The effect of atropine on the tolerance and the convulsions seen after withdrawal from forced barbital drinking in the rat. Psychopharmacology, 1978c, in pressGoogle Scholar
  26. Wahlström, G. Estimation of brain sensitivity to the convulsive effects of choline and changes induced by chronic barbital treatment in the rat. Eur. J. Pharmacol., 1978d, in pressGoogle Scholar
  27. Wahlström, G., and Larsson, R. Activity pattern and convulsions in the abstinence period after barbital treatment in the rat. Pharmacol. Biochem. Behavior, 1977, 6: 187–192CrossRefGoogle Scholar
  28. Yamamura, H.I., and Snyder, S.H. Postsynaptic localization of muscarinic cholinergic receptor binding in rat hippocampus. Brain Res., 1974, 78: 320–326PubMedCrossRefGoogle Scholar
  29. Zilversmit, D.B., Entemann, C., and Fischler, M.C. On the calculation of “turnover time” and “H:urnover rate” from experiments involving the use of labeling agents. J. gen. Physiol., 1943, 46: 325–331CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Agneta Nordberg
    • 1
    • 2
  • Göran Wahlström
    • 1
    • 2
  1. 1.Dept. of PharmacologyUniv. of Uppsala23 UppsalaSweden
  2. 2.Dept. of PharmacologyUniversity of Umeå87 UmeåSweden

Personalised recommendations