Skip to main content
SpringerLink
Log in

Alcohol and Anesthetic Actions: Are They Mediated by Lipid or Protein?

  • Chapter
Book cover Neuropharmacology of Ethanol

  • 54 Accesses

Abstract

Attempts to explain the effects of ethanol and other alcohols on the central nervous system have historically emphasized similarities between this class of drug and general anesthetics. Thus, a recent textbook of pharmacology summarizes the matter as “Despite popular belief in its stimulant properties, ethanol is entirely depressant in its actions on neurones of the central nervous system. In fact, its actions are qualitatively similar to those of a general anesthetic” (Bowman and Rand, 1980). Thus, when considered under the Meyer-Overton “rule,” the pharmacological potency of an alcohol, like some general anesthetics, is proportional to its lipophilicity, and lipophilicity is in turn directly related to the chain length and other physicochemical properties of the alcohol. Furthermore, in contrast to almost all other classes of central nervous system (CNS) drugs, neither for alcohols nor general anesthetics has it been possible to identify any membrane receptor responsible for ethanol actions on release, response to or metabolism of any specific neurotransmitters. Although no consensus mechanisms have yet emerged for how these physicochemical properties of alcohols and anesthetics actually“explain” their effects on cellular and organismic function, the inference has been that the primary sites of action of these substances takes place within the lipid matrix of the plasma membranes.

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 EPUB and 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

  • Andersson S, Cronholm T, Sjovall J (1986): Redox effects of ethanol on steroid metabolism. Alcoholism: Clin Exp Res 10:55S–63S

    Article  Google Scholar 

  • Bauche F, Bourdeaux-Jaubert AM, Giudicelli Y, Nordmann R (1987): Ethanol aiters the adenosine receptor-Ni-mediated adenylate cyclase inhibitory response in rat brain cortex in vitro. FEBS Lett 219:296–300

    Article  Google Scholar 

  • Bloom FE (1989): Neurobiology of alcohol action and alcoholism. In: Review of Psychiatry, Vol. 8. Meyer RG, ed. Washington, DC: American Psychiatry Press, pp 309–322

    Google Scholar 

  • Bloom FE, Siggins GR, Foote SL, Gruol D, Aston-Jones G, Rogers J, Pittman Q, Staunton D (1984): Noradrenergic involvement in the cellular actions of ethanol. In: Catecholamines, Neuropharmacology and Central Nervous System—Theoretical Aspects Usdin E, ed. New York: Alan R Liss Inc, pp 159–167

    Google Scholar 

  • Bode DC, Molinoff PB (1988): Effects of ethanol in vitro on the beta adrenergic receptor-coupled adenylate cyclase system. J Pharmacol Exp Ther 246:1040–1047

    Google Scholar 

  • Bowman WC, Rand MJ (1980): Textbook of Pharmacology, 2nd ed. Oxford: Blackwell Scientific Publications, pp 8.12–8.13

    Google Scholar 

  • Browning MD, Huang CK, Greengard P (1987): Similarities between protein IIIa and protein IIIb, two prominent synaptic vesicle-associated phosphoproteins. J Neurosci 7(3):847–853

    Google Scholar 

  • Corpechot C, Leclerc P, Baulieu EE, Brazeau P (1985): Neurosteroids: regulatory mechanisms in male rat brain during heterosexual exposure. Steroids 45:229–234

    Article  Google Scholar 

  • Corpechot C, Shoemaker WJ, Bloom FE (1983): Endogenous brain steroids: effect of acute ethanol ingestion. Soc Neurosci Abstr 13:1237

    Google Scholar 

  • Daly J, Fuxe K, Jonsson G (1974): 5,7-dihydroxytryptamine as a tool for the morphological and functional analysis of central 5-hydroxytryptamine neurons. Res Comm Chem Pathol Pharmacol 7:175–187

    Google Scholar 

  • Davis VE, Walsh MJ (1970): Alcohol, amines and alkaloids: a possible basis for alcohol addiction. Science 167:1005–1007

    Article  Google Scholar 

  • Fargin A, Raymond JR, Lohse MJ, Kobilka BK, Caron MG, Lefkowitz RI (1988): The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1 α receptor. Nature 335:358–360

    Article  Google Scholar 

  • Foote SL, Bloom FE, Aston-Jones G (1983): Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev 63:844–914

    Google Scholar 

  • Gallagher GL (1989): Evolutions: The plasma membrane. J NIH Res 1:131–132

    Google Scholar 

  • Gatto GJ, Murphy JM, Waller MB, McBride WJ, Lumeng L, Li TK (1987a): Chronic ethanol tolerance through free-choice drinking in the P line of alcohol-preferring rats. Pharmacol Biochem Behav 28(1):111–115

    Article  Google Scholar 

  • Gatto GJ, Murphy JM, Wal ler MB, McBride WJ, Lumeng L, Li TK (1987b) : Persistence of tolerance to a single dose of ethanol in the selectively-bred alcohol-preferring P rat. Pharmacol Biochem Behav 28(1):105–110

    Article  Google Scholar 

  • Goldstein DB (1987): Ethanol-induced adaptation in biological membranes. Ann NY Acad Sci 492:103–111

    Article  Google Scholar 

  • Gruber HJ (1988): Interaction of amphiphiles with integral membrane proteins. II. A simple, minimal model for the nonspecific interaction of amphiphiles with the anion exchanger of the erythrocyte membrane. Biochim Biophys Acta 944:425–436

    Article  Google Scholar 

  • Harris RA, Allan AM (1989): Alcohol intoxication: ion channels and genetics. FASEB Journal 3:1689–1695

    Google Scholar 

  • Harris AR, Burnett R, McQuilkin S, McClard A, Simon FR (1987): Effects of ethanol on membrane order: fluorescence studies. Ann NY Acad Sci 492:125 – 135

    Article  Google Scholar 

  • Harrison NL, Vicini S, Barker JL (1987): A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons. J Neurosci 7:604–609

    Google Scholar 

  • Hoek JB, Taraschi TF (1988): Cellular adaptation to ethanol. Trends Biochem Sci 13:269–274

    Article  Google Scholar 

  • Hoffman PL, Saito T, Tabakoff B (1987): Selective effects of ethanol on neurotransmitter receptor-effector coupling systems in different brain areas. Ann NY Acad Sci 492:396–397

    Article  Google Scholar 

  • Hu ZY, Bourreau E, Jung-Testas I, Robel P, Baulieu EE (1987): Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone. Proc Natl Acad Sci (USA) 84:8215–8219

    Article  Google Scholar 

  • Hunt WA (1985): Alcohol and Biological Membranes. New York: Guilford Press

    Google Scholar 

  • Jung-Testas I, Alliot F, Pessac B, Robel P, Baulieu EE (1989): Immunocytochemical localization of cytochrome P-450scc in cultured rat oligodendrocytes CR Acad Sci 308:165–70

    Google Scholar 

  • Koob GF, Bloom FE (1988): Cellular and molecular mechanisms of drug dependence. Science 242:715–723

    Article  Google Scholar 

  • Koob GF, Braestrup C, Thatcher-Britton K (1986): The effects of FG 7142 and RO 15–1788 on the release of punished responding produced by chlordiazepoxide and ethanol in the rat. Psychopharmacol 90:173–178

    Google Scholar 

  • Koob GF, Strecker RE, Bloom FE (1980): Effects of naloxone on the anticonflict properties of alcohol and chlordiazepoxide. Substance Alcohol Actions/Misuse 1:447–457

    Google Scholar 

  • Lambert JJ, Peters JA, Cottrell GA (1987): Actions of synthetic and endogenous steroids on the GABA receptor. TIPS 8:224–227

    Google Scholar 

  • Le Goascogne C, Robel P, Gouezou M, Sananes N, Baulieu EE, Waterman M (1987): Neurosteroids: cytochrome P-450scc in rat brain. Science 237:1212–1215

    Article  Google Scholar 

  • Lima-Landman MTR, Albuquerque EX (1989): Ethanol potentiates and blocks NMDA-activated single-channel currents in rat hippocampal pyramidal cells. Fed Eur Biochem Soc 247:61–67

    Article  Google Scholar 

  • Lovinger DM, White G, Weight FF (1989): Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243:1721–1724

    Article  Google Scholar 

  • Madamba SG, Siggins GR, Battenberg EL, Bloom FE (1987): Depletion of brainstem 5-hydroxytrypamine (5HT) suppresses the excitatory effect of systemic ethanol on inferior olivary neurons (ION). Soc Neurosci Abstr 13:501

    Google Scholar 

  • Majewska MD, Schwartz RD (1987): Pregnenolone-sulfate: an endogenous antagonist of the gamma-aminobutyric acid receptor complex in brain? Brain Res 404:355–60

    Article  Google Scholar 

  • Majewska MD, Mienville JM, Vicini S (1988): Neurosteroid pregnenolone sulfate antagonizes electrophysiological responses to GABA in neurons. Neurosci Lett 90:279–284

    Article  Google Scholar 

  • Mancillas J, Siggins GR, Bloom FE (1986a): Systemic ethanol: selective enhancement of responses to acetylcholine and somatostatin in the rat hippocampus. Science 231:161–163

    Article  Google Scholar 

  • Mancillas J, Siggins GR, Bloom FE (1986b): Somatostatin-selectively enhances acetylcholine-induced excitations in rat hippocampus and cortex. Proc Natl Acad Sci USA 83:7518–7521

    Article  Google Scholar 

  • Miller KW, Firestone LL, Forman SA (1987): General anesthetic and specific effects of ethanol on acetylcholine receptors. Ann NY Acad Sci 492:71–85

    Article  Google Scholar 

  • Mueller GC, Fleming MF, LeMahieu MA, Lybrand GS, Barry KJ (1988): Synthesis of phosphatidylethanol—a potential marker for adult males at risk for alcoholism. Proc Nat Acad Sci (USA) 85:9778–9782

    Article  Google Scholar 

  • Murphy JM, McBride WJ, Lumeng L, Li T K (1987): Contents of monoamines in forebrain regions of alcohol-preferring (P) and nonpreferring (NP) lines of rats. Pharmacol Biochem Behav 26(2):389–392

    Article  Google Scholar 

  • Murphy JM, Waller MB, Gatto WJ, Li T-K(1985): Monoamine uptake inhibitors attenuate ethanol intake in alcohol-preferring (P) rats. Alcohol 2(2):349–352

    Article  Google Scholar 

  • Myers RD (1989): Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms. Experientia 45:436

    Article  Google Scholar 

  • Nagy LE, Diamond I, Gordon A (1988): Cultured lymphocytes from alcoholic subjects have altered cAMP signal transduction. Proc Nat Acad Sci (USA) 85:6973–6976

    Article  Google Scholar 

  • Nestoros JN (1980): Ethanol specifically potentiates GABA-mediated neurotransmission in feline cerebral cortex. Science 209:708–710

    Article  Google Scholar 

  • Newlin SA, Mancillas-Trevino J, Bloom FE (1981): Ethanol causes increase in excitation and inhibition in area CA3 of the dorsal hippocampus. Brain Res 209:113–128

    Article  Google Scholar 

  • Perdahl E, Wu WC, Browning MD, Wimblad B, Greengard P (1984): Protein III, a neuron-specific phosphoprotein: variant forms found in human brain. Neurobehav Toxicol Teratol 6:425–431

    Google Scholar 

  • Pritchett DB, Sontheimer H, Shivers BD, Ymer S, Kettenman H, Schofield PR, Seburg PH (1989): Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology. Nature 338:582–585

    Article  Google Scholar 

  • Rabin RA, Bode DC, Molinoff PB (1986): Relationship between ethanol-induced alterations in fluorescence anisotropy and adenylate cyclase activity. Biochem Pharmacol 35:2331–2335

    Article  Google Scholar 

  • Rabin RA, Molinoff PB (1983): Multiple sites of action of ethanol on adenylate cyclase. J Pharmacol Exp Ther 227:551–556

    Google Scholar 

  • Rogers J, Madamba SG, Staunton DA, Siggins GR (1986): Ethanol increases single unit activity in the inferior olivary nucleus. Brain Res 385:253–262

    Article  Google Scholar 

  • Rogers J, Siggins JR, Schulman JR, Bloom, FE (1980): Physiological correlates of ethanol intoxication, tolerance, and dependence in rat cerebellar purkinje cells. Brain Res 196:183–198

    Article  Google Scholar 

  • Saito T, Lee JM, Tabakoff B (1985): Ethanol’s effects on cortical adenylate cyclase activity. J Neurochem 44:1037–1044

    Article  Google Scholar 

  • Seeman P (1972): The membrane actions of anesthetics and tranquilizers. Pharmacol Rev 24:583–655

    Google Scholar 

  • Shefner SA (1989): Electrophysiological effects of ethanol on brain neurons. In: Focus on Biochemistry and Physiology of Substance Abuse. CRC Press, Watson RR, ed. Boca Raton, Florida, pp 25–53

    Google Scholar 

  • Siggins GR, Bloom FE, French ED, Madamba SG, Mancillas J, Pittman QJ, Rogers J (1987a): Electrophysiology of ethanol on central neurons. Ann NY Acad Sci 492:350–366

    Article  Google Scholar 

  • Siggins GR, French E (1979): Central neurons are depressed by iontophoretic and micro-pressure applications of ethanol and tetrahydropapaveroline. Drug Alcohol Depend 4:239–243

    Article  Google Scholar 

  • Siggins GR, Gruol DL (1986): Synaptic mechanisms in the vertebrate central nervous system. In: Handbook of Physiology, Volume on Intrinsic Regulatory Systems of the Brain, Bloom FE, ed. Bethesda, Maryland: The American Physiological Association, pp 1–114

    Google Scholar 

  • Siggins GR, Madamba SG, Moore S (1990): Electrophysiological evaluation of acute ethanol effects on transmitter responses in central neurons. In: NIAAA Research Monograph: Initial sensitivity to ethanol. Deitrich R, Pawlowski A, eds. Keystone, Colorado, pp 197–232

    Google Scholar 

  • Siggins GR, Pittman QJ, French ED (1987b): Effects of ethanol on CA1 and CA3 pyramidal cells in the hippocampal slice preparation: an intracellular study. Brain Res 414:22–34

    Article  Google Scholar 

  • Smith BR, Amit Z (1987): False neurotransmitters and the effects of ethanol on the brain. Ann NY Acad Sci 492:384–389

    Article  Google Scholar 

  • Steinbusch HWM (1984): Serotonin-immunoreactive neurons and their projections in the CNS. In: Handbook of Chemical Neuroanatomy, Vol. 3: Classical Transmitters and Transmitter Receptors in the CNS, Part II. Aökfelt T, Björklund A, Kuhar M, eds. Elsevier Science Pub. New York, pp 68–125

    Google Scholar 

  • Tabakoff B, Hoffman PL, Liljequist S (1987): Effects of ethanol on the activity of brain enzymes. Enzyme 37:70–86

    Google Scholar 

  • Ticku MK, Burch T (1980): Alterations in GABA receptor sensitivity following acute and chronic ethanol treatments. J Neurochem 34:417–423

    Article  Google Scholar 

  • Ticku MK, Burch TP, Davis WC (1983): The interactions of ethanol with the benzodiazepine GABA receptor ionophore complex. Pharmacol Biochem Behav 18: (Suppl)15–18

    Article  Google Scholar 

  • Treistman SN, Wilson A (1987): Alkanol effects on early potassium currents in Aplysia neurons depend on chain length. Proc Natl Acad Sci (USA) 84:9299–9303

    Article  Google Scholar 

  • Turner DM, Ransom RW, Yang JS, Olsen RW (1989): Steroid anesthetics and naturally occurring analogs modulate the gamma-aminobutyric acid receptor complex at a site distinct from barbiturates. J Pharmacol Exp Ther 248:960–966

    Google Scholar 

  • Vatier OC, Bloom FE (1988): Effect of ethanol on the nerosteroids concentrations in the rat brain. Soc Neurosci Abstr 14: 195

    Google Scholar 

  • Volicer L, Gold BI (1973): Effect of ethanol on cylic AMP levels in rat brain. Life Sci 13:269–280

    Article  Google Scholar 

  • Wada K, Ballivet M, Boulter J, Connolly J, Wade E, Deneris ES, Swanson LW, Heinemann S, Patrick J (1988): Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor. Science 240:330–332

    Article  Google Scholar 

  • Weiner H (1987): Subcellular localization of acetaldehyde oxidation in liver. Ann NY Acad Sci 492:25–34

    Article  Google Scholar 

  • Wood WG, Schroeder F (1988): Membrane effects of ethanol: bulk lipid versus lipid domains. Life Sci 43:467–475

    Article  Google Scholar 

Download references

Authors
  1. Floyd E. Bloom
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Psychiatry, School of Medicine, University of Connecticut Health Center, Farmington, CT, 06032, USA

    Roger E. Meyer M.D.

  2. Department of Psychology, Howard University and O.S.A., N.I.A.A.A., Rockville, MD, 20857, USA

    Michael J. Lewis Ph.D.

  3. Research Institute of the Scripps Clinic, La Jolla, CA, 92037, USA

    George F. Koob Ph.D.

  4. N.I.H., N.I.M.H., Bethesda, MD, 20892, USA

    Steven M. Paul M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bloom, F.E. (1991). Alcohol and Anesthetic Actions: Are They Mediated by Lipid or Protein?. In: Meyer, R.E., Lewis, M.J., Koob, G.F., Paul, S.M. (eds) Neuropharmacology of Ethanol. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4757-1305-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-1305-3_1

  • Publisher Name: Birkhäuser, Boston, MA

  • Print ISBN: 978-1-4757-1307-7

  • Online ISBN: 978-1-4757-1305-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation