Summary
Recent in vitro electrophysiological studies have revealed that ethanol specifically reduces N-methyl-D-aspartate (NMDA)-activated ion currents, e.g. in hippocampal slices. In the present study, utilizing extracellular recording techniques, the effect of ethanol on excitatory amino acid induced excitability of rat locus coeruleus noradrenergic neurons was investigated in vivo. Administration of ethanol (2 g/kg, i.p.) significantly inhibited the excitation of the locus coeruleus neurons as produced by microiontophoretic application of glutamate, NMDA or quisqualate, but not that of kainate. In contrast, the locus coeruleus response to similarly applied acetylcholine was unaffected by the ethanol treatment. Although ethanol did not alter the basal firing rate of locus coeruleus neurons, the drug significantly changed the firing pattern of the neurons into a more regularized rhythm. It is proposed that the presently observed attenuation of glutamate excitation of locus coeruleus by ethanol may constitute part of the underlaying mechanism for ethanol intoxication in man.
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Aghajanian GK, Cedarbaum JM, Wang RY (1977) Evidence for norepinephrine-mediated collateral inhibition of locus coeruleus neurons. Brain Res 131: 570–577
Allan AM, Harris RA (1986) Gamma-aminobutyric acid and alcohol actions: Neurochemical studies of long sleep and short sleep mice. Life Sci 39: 2005–2015
Aston-Jones G, Ennis M, Pieribone VA, Nickell WT, Shipley MT (1986) The brain nucleus locus coeruleus: Restricted afferent control of a broad efferent network. Science 234: 734–737
Aston-Jones G, Foote SL, Bloom FE (1982) Low doses of ethanol disrupt sensory responses of brain noradrenergic neurones. Nature 296: 857–860
Engberg G (1989) Nicotine induced excitation of locus coeruleus neurons is mediated via release of excitatory amino acids. Life Sci 44: 1535–1540
Engberg G, Svensson TH (1980) Pharmacological analysis of a cholinergic receptor mediated regulation of brain nor-epinephrine neurons. J Neural Transm 49: 137–150
Engel JA, Fahlke C, Hulthe P, Hård E, Johannessen K, Sape B, Svensson L (1988) Biochemical and behavioral evidence for an interaction between ethanol and calcium channel antagonists. J Neural Transm 74: 181–193
Ennis M, Aston-Jones G (1986) A potent excitatory input to the nucleus locus coeruleus from the ventrolateral medulla. Neurosci Lett 71: 299–305
Ennis M, Aston-Jones G (1988) Activation of locus coeruleus neurons from the nucleus paragigantocellularis: a new excitatory amino acid pathway in brain. J Neuroscience 8: 3644–3657
Foote SL, Bloom FE, Aston-Jones G (1983) Nucleus locus coeruleus: new evidence of anatomical and physiological specificity. Physiol Rev 63: 844–914
Goldstein D (1983) Pharmacology of alcohol. Oxford University Press, Oxford
Gonon FG (1988) Nonlinear relationship between impulse flow and dopamine released by rat midbrain dopaminergic neurons as studied by in vivo electrochemistry. Neuroscience 24: 19–28
Gonzales RA, Woodward JJ (1990) Ethanol inhibits N-methyl-D-aspartate-stimulated [3H]norepinephrine release from rat cortical slices. J Pharmacol Exp Ther 253: 1138–1144
Göthert M, Fink K (1989) Inhibition of N-methyl-D-aspartate (NMDA)- and l-glutamate-induced noradrenaline and acetylcholine release in the brain by ethanol. Naunyn-Schmiedeberg's Arch Pharmacol 340: 516–521
Hajós M, Engberg G (1990) A role of excitatory amino acids in the activation of locus coeruleus neurons following cutaneous thermal stimuli. Brain Res 521: 325–328
Harris RA, Hood WH (1980) Inhibition of synaptosomal calcium uptake by ethanol. J Pharmacol Exp Ther 213: 562–568
Leslie SW, Barr E, Chandler J, Farrar RP (1983) Inhibition of fast and slow-phase depolarization-dependent synaptosomal calcium uptake by ethanol. J Pharmacol Exp Ther 225: 571–575
Lima-Landman MTR, Albuquerque EX (1989) Ethanol potentiates and blocks NMDA-activated single-channel currents in rat hippocampal pyramidal cells. FEBS-letters 247: 61–67
Lovinger DM, White G, Weight FF (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243: 1721–1724
Lovinger DM, White G, Weight FF (1990) NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat. J Neurosci 10: 1372–1379
Olpe H-R, Steinmann MW, Brugger F, Pozza MF (1989) Excitatory amino acid receptors in the rat locus coeruleus — an extracellular in vitro study. Naunyn-Schmiedeberg's Arch Pharmacol 339: 312–314
Pohorecky LA, Brick J (1977) Activity of neurons in the locus coeruleus of the rat: inhibition by ethanol. Brain Res 131: 174–179
Read GW, Cutting W, Furst A (1960) Comparison of excited phases after sedatives and tranquilizers. Psychopharmacologia (Berl) 1: 346–350
Suzdak PD, Schwartz RD, Skolnick P, Paul SM (1986) Ethanol stimulates γ-amonobutyric acid receptor-mediated chloride transport in rat brain synaptosomes. Proc Natl Acad Sci USA 83: 4071–4075
Svensson TH (1987) Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in brain: putative implications for psychiatry and psychopharmacology. Psychopharmacology 92: 1–7
Svensson TH, Engberg G (1980) Antagonism of ethanol's central stimulation by catecholamine receptor agonists. In: Begleiter H (ed) Advances in experimental medicine and biology, vol 126. Plenum Press, New York
Tasaki K, Tsukahara U, Ito S, Wayner MJ, Yu WY (1968) A simple, direct and rapid method for filling microelectrodes. Physiol Behav 3: 1009–1010
Tung C-S, Ugedo L, Grenhoff J, Engberg G, Svensson TH (1989) Peripheral induction of burst firing in locus coeruleus neurons by nicotine mediated via excitatory amino acids. Synapse 4: 313–318
Watkins JC, Evans RH (1981) Excitatory amino acid transmitters. Ann Rev Pharmacol Toxicol 21: 165–204
Watkins JC, Krogsgaard-Larsen P, Honoré T (1990) Structure-activity relationships in the development of excitatory amino acid receptor agonist and competitive antagonists. TIPS 11: 25–33
Werner G, Mountcastle VB (1963) The variability of central neural activity in a sensory system and its implication for the central reflection of sensory events. J Neurophysiol 26: 958–977
White G, Lovinger DM, Weight FF (1990) Ethanol inhibities NMDA-activated current but does not alter GABA-activated current in an isolated adult mammalian neuron. Brain Res 507: 332–336
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Engberg, G., Hajós, M. Ethanol attenuates the response of locus coeruleus neurons to excitatory amino acid agonists in vivo. Naunyn-Schmiedeberg's Arch Pharmacol 345, 222–226 (1992). https://doi.org/10.1007/BF00165740
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DOI: https://doi.org/10.1007/BF00165740