Skip to main content
SpringerLink
Log in

Alterations of Macromolecule Biosynthesis after Chronic Administration of Opiates and Ethanol

  • Chapter
Alcohol Intoxication and Withdrawal—IIIb

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 85B))

Abstract

The literature concerning the effects of opiates, alcohol and barbiturates on RNA and protein metabolism is reviewed. Recent findings from this laboratory suggest that chronic morphine treatment increases the template activity of chromatin from oligodendroglial nuclei while chronic ethanol treatment decreases this activity. In addition, chronic morphine treatment stimulates protein synthesis in cell free systems and may increase the synthesis of discrete synaptic membrane proteins. Results from other laboratories suggest a general decrease in macromolecule biosynthesis with long term ethanol consumption. These results are discussed in terms of the possible roles of protein synthesis in the effects of chronic opiate and ethanol administration.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Allfrey, V.G. Some observations on histone acetylation and its temporal relationship to gene activation. In A. San Pietro, M.R. Lanborg and F.T. Kenney (Eds.) Regulatory Mechanisms for Protein Synthesis in Mammalian Cells, pp. 65–100, New York, Academic Press, 1968.

    Google Scholar 

  • Banker, G. and Cotman, C.W. Characteristics of different amino acids as protein precursors in mouse brain: advantages of certain carboxyl-labeled amino acids. Arch. Biochem. Biophys., 142:565–573, 1971.

    Article  Google Scholar 

  • Barondes, S.H. and Dutton, C.R. Protein metabolism in the nervous system. In R.W. Albers, C.J. Siegel, R. Katzman and B.W. Agranoff (Eds.) Basic Neurochemistry, pp. 229–244. Boston, Little Brown & Co., 1972.

    Google Scholar 

  • Becker, F.F., Rossman, T., Reiss, B. and Simon, E.J. The effect of levorphanol tartrate on ribonucleic acid synthesis in normal and regenerating rat liver. Res. Commun. Chem. Path. Pharmacol., 3:105–116, 1972.

    Google Scholar 

  • Berl, S. and Clark, D.D. Compartmentalization of amino acid metabolism. In A. Lajtha (Ed.) Handbook of Neurochemistry, Vol. II, pp. 447–472. New York, Plenum Press, 1969.

    Google Scholar 

  • Castles, T.R., Campbell, S., Gouge, R. and Lee, C.C. Nucleic acid synthesis in brains from rats tolerant to morphine analgesia. J. Pharmacol. Exp. Ther., 181:399–406, 1972.

    Google Scholar 

  • Chaplin, E.R., Goldberg, A.L. and Diamond, I. Leucine oxidation in brain slices and nerve endings. J. Neurochem. 26:701–707, 1976.

    Article  Google Scholar 

  • Chuang, D.M., Hollenbeck, R. and Costa, E. Enhanced template activity in chromatin from adrenal medulla after phosphorylation of chromosomal proteins. Science, 193:60–62, 1976.

    Article  Google Scholar 

  • Clouet, D.H. The effects of drugs on protein synthesis in the nervous system. In A. Lajtha (Ed.) Protein Metabolism of the Nervous System, pp. 699–713. New York, Plenum Press, 1970.

    Chapter  Google Scholar 

  • Clouet, D.H. Protein and nucleic acid metabolism. In D.H. Clouet (Ed.) Narcotic Drugs: Biochemical Pharmacology, pp. 216–228. New York, Plenum Press, 1971.

    Google Scholar 

  • Clouet, D.H. and Ratner, M. The effect of the administration of morphine on the incorporation of (l4C)-leucine into the proteins of rat brain in vivo. Brain Res., 4:33–43, 1967.

    Article  Google Scholar 

  • Clouet, D.H. and Ratner, M. The effect of morphine administration on the incorporation of (14C)-leucine into protein in cell-free systems from rat brain and liver. J. Neuroehem., 15:17–23, 1968.

    Article  Google Scholar 

  • Cohen, M., Keats, A.S., Krivoy, W. and Ungar, G. Effect of actinomycin-D on morphine tolerance. Proc. Soc. Exp. Biol. Med., 119:381–384, 1965.

    Google Scholar 

  • Collier, H.O.J., Hammond, M.D. and Schneider, C. Effects of drugs affecting endogenous amines or cyclic nucleotides on ethanol withdrawal head twitches in mice. Brit. J. Pharmacol., 58:9–16, 1976.

    Article  Google Scholar 

  • Cox, B.M., Ginsberg, M. and Osman, O.H. Acute tolerance to narcotic analgesic drugs in rat. Brit. J. Pharmacol., 33:245–256, 1968.

    Google Scholar 

  • Cox, B.M. and Osman, O.H. Inhibition of development of tolerance to morphine in rats by drugs which inhibit ribonucleic acid or protein synthesis. Brit. J. Pharmacol., 38:157–170, 1970.

    Article  Google Scholar 

  • Craves, F.B., Meyerhoff, J.L., Loh, H.H. and Trevor, A.J. Effect of morphine on a cell free protein synthetic system isolated from mouse brain. Fed. Proc., 34:2921, 1975.

    Google Scholar 

  • Darnell, J.E., Philipson, L., Wall, R. and Adesnik, M. Polyadenylic acid sequences: role in conversion of nuclear RNA into messenger RNA. Science, 174:507–510, 1971.

    Article  Google Scholar 

  • Datta, R.K. and Antopol, W. Effects of morphine on mouse liver and brain ribonuclease and deoxyribonuclease activities. Tox. Appl. Pharmacol., 18:851–855, 1971.

    Article  Google Scholar 

  • Datta, R.K. and Antopol, W. Inhibitory effects of chronic administration of morphine on uridine and thymidine incorporating abilities of mouse liver and brain subcellular fractions. Tox. Appl. Pharmacol., 23:75–81, 1972.

    Article  Google Scholar 

  • Datta, R.K. and Antopol, W. Influence of methadone and sulfa-pyridine on mouse liver and brain ribonuclease and deoxyribonuclease. Pharmacology, 9:97–106, 1973a.’

    Article  Google Scholar 

  • Datta, R.K. and Antopol, W. Inhibitory effect of chronic administration of morphine on RNA polymerase activities of mouse liver and brain nuclei. Tox. Appl. Pharmacol., 25:71–76, 1973b.

    Article  Google Scholar 

  • Datta, R.K. and Antopol, W. Effect of chronic administration of morphine on mouse brain aminoacyl-tRNA synthetase and tRNA-amino acid binding. Brain Res., 53:373–386, 1973c.

    Article  Google Scholar 

  • DeLarco, J-, Abramowitz, A., Bromwell, K. and Curoff, G. Polyadenylic acid-containing RNA from rat brain. J. Neurochem., 24:215–222, 1976.

    Article  Google Scholar 

  • Dunn, A.J. The chemistry of learning and the formation of memory. In W.H. Gispen (Ed.) Molecular and Functional Neurobiology, pp. 347–387. Amsterdam, Elsevier, 1976.

    Google Scholar 

  • Dunn, A.J. and Bondy, S.C. Functional Chemistry of the Brain. New York, Spectrum Publications, 1974.

    Google Scholar 

  • Fehr, K.A., Kalant, H. and LeBlanc, A.E. Residual learning deficit after heavy exposure to cannabis or alcohol in rats. Science, 192:1249–1251, 1976.

    Article  Google Scholar 

  • Feinberg, M.P. and Cochin, J. Inhibition of development of tolerance to morphine by cycloheximide. Biochem. Pharmacol., 21:3082–3085, 1972.

    Article  Google Scholar 

  • Fleming, E.W., Tewari, S. and Noble, E.P. Effects of chronic ethanol ingestion on brain aminoacyl-tRNA synthetases and tRNA. J. Neurochem., 24:553–560, 1975.

    Article  Google Scholar 

  • Franklin, G.I. and Cox, B.M. Incorporation of amino acids into proteins of synaptosomal membranes during morphine treatment. J. Neurochem., 19:1821–1823, 1972.

    Article  Google Scholar 

  • Glassman, E. The biochemistry of learning: an evaluation of the role of RNA and protein. Ann. Rev. Biochem., 38:605–646, 1969.

    Article  Google Scholar 

  • Goldstein, D.B. Relationship of alcohol dose to intensity of withdrawal signs in mice. J. Pharmacol. Exp. Ther. 180:203–215, 1972.

    Google Scholar 

  • Goldstein, D.B. Pharmacological aspects of physical dependence on ethanol. Life Sci., 18:553–562, 1976.

    Article  Google Scholar 

  • Hahn, D.L. and Goldstein, A. Amounts and turnover rates of brain proteins in morphine-tolerant mice. J. Neurochem., 18:1887–1893, 1971.

    Article  Google Scholar 

  • Harris, R.A., Dunn, A. and Harris, L.S. Effects of acute and chronic morphine administration on the incorporation of (3H)-lysine into mouse brain and liver proteins. Res. Comm. Chem. Path. Pharmacol., 9:299–306, 1974.

    Google Scholar 

  • Harris, R.A., Harris, L.S. and Dunn, A. Effects of narcotic drugs on ribonucleic acid and nucleotide metabolism in mouse brain. J. Pharmacol. Exp. Ther., 192:280–287, 1975.

    Google Scholar 

  • Hitzemann, R.J. and Loh, H.H. Effect of chronic morphine and pentobarbital treatment on synaptic plasma membrane protein synthesis. Proceedings of the NAS-NRC Committee on Problems of Drug Dependence, pp. 460–473, 1974.

    Google Scholar 

  • Hitzemann, R.J. and Loh, H.H. On the possible role of brain protein synthesis in functional barbiturate tolerance. Eur. J. Pharmacol., 40:163–173, 1976a.

    Article  Google Scholar 

  • Hitzemann, R.J. and Loh, H.H. Influence of morphine on protein synthesis in discrete subcellular fractions of the rat brain. Res. Comm. Chem. Path. Pharmacol., 14:237–248, 1976b.

    Google Scholar 

  • Ho, I.K. Systematic assessment of tolerance to pentobarbital by pellet implantation. J. Pharmacol. Exp. Ther., 197:479–487, 1976.

    Google Scholar 

  • Hodgson, J.R., Lee, C-C. and Castles, T.R. Brain chromatin activity of morphine-treated rats. Proc. Soc. Biol. Exp. Med., 141:790–793, 1972.

    Google Scholar 

  • Hogans, A.F., Guroff, G. and Udenfriend, S. Studies on the origin of pyrimidines for biosynthesis of neural RNA in the rat. J. Neurochem., 18:1699–1710, 1971.

    Article  Google Scholar 

  • Hunter, B.E., Riley, J.N., Walker, D.W. and Freund, G. Ethanol dependence in the rat: a parametric analysis. Pharmacol. Biochem. Behav., 3:619–629, 1975.

    Article  Google Scholar 

  • Jarlstedt, J. Experimental alcoholism in rats: protein synthesis in subcellular fractions from cerebellum, cerebral cortex and liver after long term treatment. J. Neurochem., 19:603–608, 1972.

    Article  Google Scholar 

  • Jarlstedt, J. and Hamberger, A. Experimental alcoholism in rats. Effect of acute ethanol intoxication on the in vitro incorporation of (3H)-leucine into neuronal and glial proteins. J. Neurochem., 19:2299–2316, 1972.

    Article  Google Scholar 

  • Kalant, H., LeBlanc, A.E. and Gibbins, R.J. Tolerance and dependence on some non-opiate psychotropic drugs. Pharmacol. Rev., 23:135–191, 1971.

    Google Scholar 

  • Koenig, H. Neurobiological action of some pyrimidine analogs. Int. Rev. Neurobiol., 10:199–230, 1967.

    Article  Google Scholar 

  • Kuriyama, K., Sze, P.Y. and Rauscher, G.E. Effects of acute and chronic ethanol administration on ribosomal protein synthesis in mouse brain and liver. Life Sci., 10:II, 181–189, 1971.

    Article  Google Scholar 

  • Kuschinsky, K. Effect of morphine on protein synthesis in synapto-somes and mitochondria of mouse brain in vivo. Naunyn Schmiedebergs Arch. Pharmak., 271:294–300, 1971.

    Article  Google Scholar 

  • Lajtha, A. Protein Metabolism of the Nervous System. New York, Plenum Press, 1970.

    Google Scholar 

  • Lajtha, A. and Marks, N. Protein turnover. In A. Lajtha (Ed.) Handbook of Neurochemistry, Vol. VB, pp. 551–630. New York, Plenum Press, 1971.

    Google Scholar 

  • Lang, D.W., Darrah, H.K., Hedley-Whyte, J. and Laasberg, L.H. Uptake into brain proteins of 35s-methionine during morphine tolerance. J. Pharmacol. Exp. Ther., 192:521–530, 1975.

    Google Scholar 

  • Langan, T.A. Phosphorylation of proteins of the cell nucleus. In A. San Pietro, M.R. Lanborg and F.T. Kenney (Eds.) Regulatory Mechanisms for Protein Synthesis in Mammalian Cells, pp. 101–118. New York, Academic Press, 1968.

    Google Scholar 

  • LeBlanc, A.E., Kalant, H., Gibbins, R.J. and Berman, N.D. Acquisition and loss of tolerance to ethanol by the rat. J. Pharmacol. Exp. Ther., 168:244–250, 1969.

    Google Scholar 

  • LeBlanc, A.E., Matsunaga, M. and Kalant, H. Effects of frontal polar cortical ablation and cycloheximide on ethanol tolerance in rats. Pharmacol. Biochem. Behav., 4:175–179, 1976.

    Article  Google Scholar 

  • Lee, N.M., Ho, I.K. and Loh, H.H. Effect of chronic morphine treatment on brain chromatin template activities in mice. Biochem. Pharmacol., 24:1983–1987, 1975.

    Article  Google Scholar 

  • Lee, N.M. and Loh, H.H. A study of deoxyribonucleic acid binding of narcotic analgesics. Biochem. Pharmacol., 24:1249–1251, 1975.

    Article  Google Scholar 

  • Loh, H.H. and Hitzemann, R.J. Effect of morphine on the turnover and synthesis of (leu-3H)-protein and (Ch-14C)-phosphatidylcholine in discrete regions of the rat brain. Biochem. Pharmacol., 23:1753–1765, 1974.

    Article  Google Scholar 

  • Loh, H.H., Shen, F. and Way, E.L. Inhibition of morphine tolerance and physical dependence development and brain serotonin synthesis by cycloheximide. Biochem. Pharmacol., 18:2711–2721, 1969.

    Article  Google Scholar 

  • Loh, H.H., Shen, F-H. and Way, E.L. Effect of dactinomycin on the acute toxicity and brain uptake of morphine. J. Pharmacol. Exp. Ther., 177:326–331, 1971.

    Google Scholar 

  • Luthra, Y.K., Rosenkrantz, H., Heyman, I.A. and Braude, M.C. Differential neurochemistry and temporal pattern in rats treated orally with Δ9-tetrahydrocannabinol for periods up to six months. Tox. Appl. Pharmacol., 32:418–431, 1975.

    Article  Google Scholar 

  • Mahler, H. Nucleic acid metabolism. In R.W. Albers, G.J. Siegel, R. Katzman and B.W. Agranoff (Eds.) Basic Neurochemistry, pp. 245–265. Boston, Little, Brown & Co., 1972.

    Google Scholar 

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

    Article  Google Scholar 

  • Mandel, P. Free nucleotides. In A. Lajtha (Ed.) Handbook of Neurochemistry, Vol. 5, pp. 249–281. New York, Plenum Press, 1971.

    Google Scholar 

  • Marks, N. and Lajtha, A. Protein and polypeptide breakdown. In A. Lajtha (Ed.) Handbook of Neurochemistry, Vol. VA, pp. 49–139. New York, Plenum Press, 1971.

    Google Scholar 

  • McEwen, B.S. and Zigmond, R.E. Isolation of brain nuclei. In N. Marks and R. Rodnight (Eds.) Research Methods in Neurochemistry, pp. 139–161. New York, Plenum Press, 1972.

    Chapter  Google Scholar 

  • McMillan, D.E., Waddell, F.B. and Cathcart, C.F. Establishment of physical dependence in mice by oral ingestion of morphine. J. Pharmacol. Exp. Ther., 190:416–419, 1974.

    Google Scholar 

  • Morland, J. and Sjetnan, A.E. Reduced incorporation of (3H)-leucine into cerebral proteins after long-term ethanol treatment. Biochem. Pharmacol., 25:220–221, 1976.

    Article  Google Scholar 

  • Navon, S. and Lajtha, A. Uptake of morphine in particulate fractions from rat brain. Brain Res., 24:534–536, 1970.

    Article  Google Scholar 

  • Noble, E.P. and Tewari, S. Protein and ribonucleic acid metabolism in brains of mice following chronic alcohol consumption. Ann. N.Y. Acad. Sci., 215:333–345, 1973.

    Article  Google Scholar 

  • Noble, E.P. and Tewari, S. Ethanol and brain ribosomes. Fed. Proc., 34:1942–1947, 1975.

    Google Scholar 

  • Oguri, K., Lee, N.M. and Loh, H.H. Apparent protein kinase activity in oligodendroglial chromatin after chronic morphine treatment. Biochem. Pharmacol., 25:2371–2376, 1976.

    Article  Google Scholar 

  • Oja, S.S. Comments on the measurement of protein synthesis in the brain. Int. J. Neuroscience, 5:31–33, 1973.

    Article  Google Scholar 

  • Renis, M., Giovine, A. and Bertolino, A. Protein synthesis in mitochondrial and microsomal fractions from rat brain and liver after acute or chronic ethanol administration. Life Sci., 16:1447–1458, 1975.

    Article  Google Scholar 

  • Schimke, R.T. Principles underlying the regulation of synthesis and degradation of protein in animal tissues. In F.O. Schmitt and F.G. Worden (Eds.) The Neurosciences, Third Study Program, pp. 813–825. Cambridge, Mass., MIT Press, 1974.

    Google Scholar 

  • Shuster, L. and Hannam, R.V. The indirect inhibition of protein synthesis in vivo by chlorpromazine. J. Biol. Chem., 239:3401–3406, 1964.

    Google Scholar 

  • Shuster, L. Tolerance and physical dependence. In D.H. Clouet (Ed.) Narcotic Drugs: Biochemical Pharmacology, pp. 408–423. New York, Plenum Press, 1971.

    Google Scholar 

  • Shuster, L., Hannam, R.V. and Boyle, W.E., Jr. A simple method for producing tolerance to dihydromorphinone in mice. J. Pharmacol. Exp. Ther., 140:149–154, 1963.

    Google Scholar 

  • Siew, C. and Goldstein, D.B. A novel method for rapid development of barbiturate tolerance and physical dependence. Fed. Proc., 35:356, 1976.

    Google Scholar 

  • Soeiro, R., Vaughan, M.H., Warner, J.R. and Darnell, J.E. The turnover of nuclear DNA-like RNA in HeLa cells. J. Cell. Biol., 39:112–118, 1968.

    Article  Google Scholar 

  • Spoerlein, M.T. and Scrafani, J. Effects of time and 8-azaguanine on the development of morphine tolerance. Life Sci., 6:1549–1564, 1967.

    Article  Google Scholar 

  • Stein, G.S., Speisberg, T.C. and Kleinsmith, L.J. Nonhistone chromosomal proteins and gene regulation. Science, 183:817–824, 1974.

    Article  Google Scholar 

  • Stolman, S. and Loh, H.H. Proceedings of the NAS-NRC Committee on Problems of Drug Dependence, 1:803–814, 1971.

    Google Scholar 

  • Stolman, S. and Loh, H.H. Stabilization of brain free polysomes by morphine. Res. Comm. Chem. Path. Pharmacol., 12:419–425, 1975.

    Google Scholar 

  • Tamerin, J.S., Weiner, S., Poppen, R., Steinglass, P. and Mendelson, J.H. Alcohol and memory. Am. J. Psychiat., 127: 1659–1664, 1971.

    Google Scholar 

  • Teiger, D.G. Induction of physical dependence on morphine, codeine and meperidine in the rat by continuous infusion. J. Pharmacol. Exp. Ther., 190:408–415, 1974.

    Google Scholar 

  • Tewari, S., Fleming, E.W. and Noble, E.P. Alterations in brain RNA metabolism following chronic ethanol ingestion. J. Neurochem., 24:561–569, 1975.

    Article  Google Scholar 

  • Tewari, S. and Noble, E.P. Ethanol and brain protein synthesis. Brain Res., 26:469–474, 1971.

    Google Scholar 

  • Tewari, S. and Noble, E.P. Chronic ethanol ingestion by rodents: effects on brain RNA. In M.A. Rothschild, M. Oratz and S.S. Schreiber (Eds.) Alcohol and Abnormal Protein Synthesis, pp. 421–448. New York, Pergamon Press, 1974.

    Google Scholar 

  • Tiplady, B. Brain protein metabolism and environmental stimulation: effects of forced exercise. Brain Res., 43:215–225, 1972.

    Article  Google Scholar 

  • Tremblay, G.C., Jimenez, U. and Crandall, D.E. Pyrimidine biosynthesis and its regulation in the developing rat brain. J. Neurochem., 26:57–64, 1976.

    Google Scholar 

  • Tseng, J.K. and Gurpide, E. Compartmentalization of aridine and uridine 5′-monophosphate in rat liver slices. J. Biol. Chem., 248:5634–5640, 1973.

    Google Scholar 

  • Walker, D.W. and Freund, G. Impairment of timing behavior after prolonged alcohol consumption in rats. Science, 182:597–599, 1973.

    Article  Google Scholar 

  • Way, E.L., Loh, H.H. and Shen, F.H. Simultaneous quantitative assessment of morphine tolerance and physical dependence. J. Pharmacol. Exp. Ther., 167:1–8, 1969.

    Google Scholar 

  • Wei, E., Loh, H.H. and Way, E.L. Quantitative aspects of precipitated abstinence in morphine dependent rats. J. Pharmacol. Exp. Ther., 184:398–403, 1973.

    Google Scholar 

  • Yamamoto, I., Inoki, R., Tamari, Y. and Iwatsubo, K. Inhibitory effect of 8-azaguanine on the development of tolerance in the analgesic action of morphine. Jap. J. Pharmacol., 17:140–142, 1967.

    Article  Google Scholar 

Download references

Author information

Author notes

  1. R. Adron Harris

    Present address: Department of Pharmacology, University of Missouri Medical Center, Columbia, Missouri, 65201, USA

Authors and Affiliations

  1. Department of Pharmacology and Langley Porter Neuropsychiatric Institute, University of California, San Francisco, California, 94143, USA

    Horace H. Loh, Nancy M. Lee & R. Adron Harris

Authors
  1. Horace H. Loh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nancy M. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Adron Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Downstate Medical Center, State University of New York, Brooklyn, New York, USA

    Milton M. Gross

Rights and permissions

Reprints and permissions

Copyright information

© 1977 Plenum Press, New York

About this chapter

Cite this chapter

Loh, H.H., Lee, N.M., Harris, R.A. (1977). Alterations of Macromolecule Biosynthesis after Chronic Administration of Opiates and Ethanol. In: Gross, M.M. (eds) Alcohol Intoxication and Withdrawal—IIIb. Advances in Experimental Medicine and Biology, vol 85B. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9038-5_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-9038-5_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-9040-8

  • Online ISBN: 978-1-4615-9038-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation