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Effect of ethanol on GABA uptake and release from hypothalamic fragments

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Abstract

A study was performed on the effect of ethanol on the basal and K+-evoked efflux of endogenous GABA from rat hypothalamic fragments. The amount of GABA present in the medium and in the tissue was measured by radioreceptor assay. In vitro addition of ethanol (50 and 100 mM) enhanced the K+-evoked efflux of GABA in a Ca++-dependent manner, and increased tissue GABA content. Since K+-evoked outflow induced by ethanol was not affected by the presence of nipecotic acid, ethanol appears to alter the uptake of endogenous GABA. An inhibitory effect of ethanol on 3H-GABA uptake was observed under K+ depolarization. On the other hand, acute ethanol administration produced a decrease in basal and K+-evoked efflux from hypothalamic fragments and in tissue GABA concentration. Changes in GABA efflux may lie behind some of the neuropharmacological effects of ethanol.

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References

  • Bernasconi R, Bittiger H, Heid J, Martin P (1980) Determination of GABA levels by a 3H-muscimol radioreceptor assay. J Neurochem 34:614–618

    Google Scholar 

  • Bowery NG, Price GW, Hudson AL, Hill DR, Wilkin GP, Turnbull MJ (1984) Visualization of different receptor types in the mammalian CNS. Neuropharmacology 23:219–231

    Google Scholar 

  • Carlen PL, Gurevich N, Durand D (1982) Ethanol in low doses augment calcium-mediated mechanisms measured intracellularly in hippocampal neurons. Science 215:306–309

    Google Scholar 

  • Cicero TJ, Meyer ER, Bell RD (1979) Effects of ethanol on the hypothalamic-pituitary-luteinizing hormone axis and testicular steroidogenesis. J Pharmacol Exp Ther 208:210–215

    Google Scholar 

  • Cuello AC, Horn AS, MacKay AVP, Iversen LL (1973) Catecholamines in the median eminence: new evidence for a major noradrenergic input. Nature 243:465–467

    Google Scholar 

  • Duvilanski BH, Seilicovich A, Diaz MC, Lasaga M, Debeljuk L (1987a) The effect of prolactin on glutamate decarboxylase activity and GABA concentration in hypothalamic slices. Psychoneuroendocrinology 12:107–116

    Google Scholar 

  • Duvilanski BH, Seilicovich A, Lasaga M, Díaz MC, Debeljuk L (1987b) Mechanism of endogenous GABA release from hypothalamic fragments. Effect of prolactin. Neuroendocrinology 46:504–510

    Google Scholar 

  • Enna SJ, Wood JH, Snyder SH (1977) Gamma aminobutiric acid (GABA) in human cerebrospinal fluid, radioreceptor assay. J Neurochem 28:1121–1124

    Google Scholar 

  • Fagg GE, Lane JD (1979) The uptake and release of putative aminoacid neurotransmitters. Neuroscience 4:1015–1036

    Google Scholar 

  • Goldstein DB (1984) The effects of drugs on membrane fluidity. Annu Rev Pharmacol Toxicol 24:43–64

    Google Scholar 

  • Greenberg DA, Cooper EC, Gordon A, Diamond I (1984) Ethanol and the γ-aminobutyric acid-benzodiazepine receptor complex. J Neurochem 42:1062–1068

    Google Scholar 

  • Gysling K, Bustos G, Concha I, Martinez P (1976) Effect of ethanol on dopamine synthesis and release from rat corpus striatum. Biochem Pharmacol 25:157–162

    Google Scholar 

  • Harris DP, Sinclair JG (1984) Ethanol-GABA interactions at the rat Purkinje cells. Gen Pharmacol 15:449–454

    Google Scholar 

  • Hyatt MC, Tyce GM (1985) The effects of ethanol on the efflux and release of norepinephrine and 5α-hydroxytryptamine from slices of rat hypothalamus. Brain Res 337:255–262

    Google Scholar 

  • Iversen LL, Mitchell JF, Srinivasan V (1971) The release of γ-aminobutyric acid during inhibition in the cat visual cortex. J Physiol (Lond) 212:519–534

    Google Scholar 

  • Krosgaard-Larsen P, Johnston GAR (1975) Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxazoles and related compounds. J Neurochem 25:797–802

    Google Scholar 

  • Kulonen E (1983) Ethanol and GABA. Med Biol 61:147–167

    Google Scholar 

  • Lace JW, Schneider CW, Hartline RA (1986) The ethanol sensitivity of calcium taken up by a depolarization-dependent process in mouse strains DBA and C57B1. Pharmacol Biochem Behav 24:1137–1139

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • McCann SM, Vijayan A, Negro-Vilar A, Mizunuma H, Mangat H (1984) Gamma aminobutyric acid (GABA), a modulator of anterior pituitary hormone secretion by hypothalamic and pituitary action. Psychoneuroendocrinology 9:97–106

    Google Scholar 

  • Magruder JD, Waid-Jones M, Reitz RC (1985) Ethanol-induced alterations in rat synaptosomal plasma membrane phospholipids. Mol Pharmacol 27:256–262

    Google Scholar 

  • Miyahara JT, Esplin DW, Zablocka B (1966) Differential effects of depressant drugs on presynaptic inhibition. J Pharmacol Exp Ther 154:119–127

    Google Scholar 

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

    Google Scholar 

  • Pearce BR, Dutton GR (1981) K+ stimulated release of endogenous glutamate, GABA and other aminoacids from neuron- and glia-enriched cultures of the rat cerebellum. FEBS Lett 135:215–218

    Google Scholar 

  • Roach MK, Davis DL, Pennington W, Nordyke E (1973) Effect of ethanol on the uptake by rat brain synaptosomes of [3H]-dl-norepinephrine, [3H]5-hydroxytryptamine, [3H]GABA and [3H]glutamate. Life Sci 12:433–441

    Google Scholar 

  • Rohde BH, Harris RA (1983) Effects of barbiturates and ethanol on muscimol-induced release of [3H]-d-aspartate from rodent cerebellum. Neuropharmacology 22:721–727

    Google Scholar 

  • Seilicovich A, Duvilanski B, Gonzalez NN, Rettori V, Mitridate de Novara A, Muñoz Maines V, Fiszer de Plazas S (1985) The effect of acute ethanol administration on GABA receptor binding in cerebellum and hypothalamus. Eur J Pharmacol 111:365–369

    Google Scholar 

  • Seilicovich A, Duvilanski BH, Díaz MC, Lasaga M, Carbini LA (1986) Ethanol and hypothalamic GABAergic system. In: Racagni G, Donoso AO (eds) Advances in biochemical psychopharmacology, vol 42. Raven Press, New York, pp 209–218

    Google Scholar 

  • Simler S, Clement J, Ciesielski L, Mandel P (1986) Brain γ-aminobutyric acid turnover rates after spontaneous chronic ethanol intake and withdrawal in discrete brain areas of C57 mice. J Neurochem 47:1942–1947

    Google Scholar 

  • Strong R, Gibson Wood W (1984) Membrane properties and aging: in vivo and in vitro effects of ethanol on synaptosomal γ-aminobutyric acid (GABA) release. J Pharmacol Exp Ther 229:726–730

    Google Scholar 

  • Suzdak PD, Schwartz RD, Skolnick P, Paul SM (1986) Ethanol γ-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes. Proc Natl Acad Sci USA 83:4071–4075

    Google Scholar 

  • Szerb JC (1982) Effect of nipecotic acid, a γ-aminobutyric acid transport inhibitor, on the turnover and release of γ-aminobutyric acid in rat cortical slices. J Neurochem 39:850–858

    Google Scholar 

  • Szerb JC (1983) Mechanism of GABA release. In: Glutamine, glutamate and GABA in the central nervous system. Liss, New York, pp 457–472

    Google Scholar 

  • Tapia R (1983) γ-Aminobutyric acid. Metabolism and biochemistry of synaptic transmission. In: Lajtha A (ed) Handbook of neurochemistry, vol 3. Plenum Press, New York, pp 375–466

    Google Scholar 

  • Ticku MK (1980) The effects of acute and chronic ethanol administration and its withdrawal on γ-aminobutyric acid receptor binding in rat brain. Br J Pharmacol 70:403–410

    Google Scholar 

  • Winer BJ (1971) Statistical principles in experimental design. McGraw Hill, New York

    Google Scholar 

  • Yoneda Y, Kanmori K, Takahahsi M, Zuo PP, Paik IH, Kuriyama K (1984) Preferential release of newly synthesized [3H]GABA from striatal slices to preloaded [3H]GABA. Neurochem Int 6:641–649

    Google Scholar 

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Seilicovich, A., Duvilanski, B.H., Lasaga, M. et al. Effect of ethanol on GABA uptake and release from hypothalamic fragments. Psychopharmacology 95, 418–422 (1988). https://doi.org/10.1007/BF00181959

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  • DOI: https://doi.org/10.1007/BF00181959

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