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Modification of GABA turnover in the striatum and hippocampus of the rat after zopiclone

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Summary

The effects of zopiclone, a non-benzodiazepine compound that interacts with benzodiazepine receptors, on GABA turnover rate and GABA content in the rat striatum and hippocampus have been studied. Intraperitoneal administration of zopiclone reduced the GABA turnover rates in both the striatum and hippocampus, as estimated from the rate of GABA accumulation after inhibition of GABA transaminase by aminooxyacetic acid (AOAA). The effect of zopiclone on AOAA-induced accumulation of GABA in the hippocampus and striatum was blocked by the intraperitoneal injection of the benzodiazepine receptor antagonist Ro 15-3505. Furthermore, zopiclone slightly but significantly decreased GABA content in the hippocampus, the decrease being blocked by coadministration of the benzodiazepine receptor antagonist Ro 15-1788. Our results confirm that the GABAergic system plays a role in the mechanism of action of zopiclone.

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References

  • Bernasconi R, Maitre L, Martin P, Raschdorf F (1982) The use of inhibitors of GABA transaminase for the determination of GABA turnover in mouse brain regions: an evaluation of aminooxyacetic acid and gabaculine. J Neurochemistry 38:57–66

    Google Scholar 

  • Blanchard JC, Boireau A, Garret C, Julou L (1979) In vitro and in vivo inhibition by zopiclone of benzodiazepine binding to rodent brain receptors. Life Sci 24:2417–2420

    Google Scholar 

  • Blanchard JC, Boireau A, Julou L (1983) Brain receptors and zopiclone. Pharmacology 27 (Suppl 2):59–69

    Google Scholar 

  • Blanchard JC, Zundel JL, Julou L (1983) Differences between cyclopyrrolone (suriclone and zopiclone) and benzodiazepine binding to rat hippocampus photolabelled membranes. Biochem Pharmacol 32:3651–3653

    Google Scholar 

  • DeFeudis FV (1982) GABAergic analgesia — a naloxone-insensitive system. Pharmacol Res Commun 14:383–390

    Google Scholar 

  • DeFeudis FV (1983) Psychoactive agents and GABA-receptors. Pharmacol Res Commun 15:29–39

    Google Scholar 

  • Duncan DB (1955) Multiple range and multiple F tests. Biometrics 11:1–42

    Google Scholar 

  • Dunnett CW (1964) New table for multiple comparison with a control. Biometrics 20:482–491

    Google Scholar 

  • Enna SJ (1981) GABA receptor pharmacology. Biochem Pharmacol 30:907–913

    Google Scholar 

  • Haefely W (1983) Antagonists of benzodiazepines: functional aspects. In: Biggio G, Costa E (eds) Benzodiazepines recognition ligands: Biochemistry and pharmacology. Raven Press, New York, pp 73–93

    Google Scholar 

  • Hunkeler W, Möhler H, Pieri L, Polc P, Bonetti EP, Cumin R, Shaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:514–516

    Google Scholar 

  • Kennedy BP, Leonard BE (1982) Effects of clobazam and other benzodiazepines on γ-aminobutyric acid turnover in stressful and non stressful situation. Drug Dev Res (Suppl 1):101

  • Julou L, Blanchard JC, Dreyfus JF (1985) Pharmacological and chemical studies of cyclopyrrolones: zopiclone and suriclone. Pharmacol Biochem Behav 23:653–659

    Google Scholar 

  • Löscher W (1981) Correlation between alterations in brain metabolism and seizure excitability following administration of GABA aminotransferase inhibitors and valproic acid-a-re-evaluation. Neurochem Int 3:397–404

    Google Scholar 

  • Mao CC, Marco E, Revuelta A, Bertilson L, Costa E (1977) The turnover rate of γ-aminobutyric acid in the nuclei of telencephalon: Implications in the pharmacology of anti-psychotics and of a minor tranquilizer. Biological Psychiatry 3:359–371

    Google Scholar 

  • Möhler H, Okada T (1977) Benzodiazepine receptor: demonstration in the central nervous system. Science 198:849–851

    Google Scholar 

  • Olsen RW (1981) GABA-benzodiazepine-barbiturate receptor interactions. J Neurochemistry 37:1–13

    Google Scholar 

  • Sanger DJ, Joly D, Zivkovic (1985) Behavioral effects of non benzodiazepine anxiolytic drugs: a comparison of CGS 9896 and zopiclone with chlordiazepoxide. J Pharmacol Exp Ther 232:831–837

    Google Scholar 

  • Sperk G, Schlogl E (1979) Reduction of number of benzodiazepine binding sites in the caudate nucleus of the rat after kainic acid injections. Brain Res 170:563–567

    Google Scholar 

  • Storm-Mathisen J (1972) Glutamate decarboxylase in the rat hippocampal region after lesion of the afferent fibre system. Evidence that the enzyme is localized in intrinsic neurons. Brain Res 40:215–235

    Google Scholar 

  • Zambotti F, Zonta N, Ferrario P, Zecca L, Mantegazza P (1986) Effects of 2-chloroadenosine on hippocampal GABA content and turnover. J Neural Transmission 65:167–175

    Google Scholar 

  • Zecca L, Zambotti F, Zonta N, Mantegazza P (1982) Determination of γ-aminobutyric acid in brain areas by high-performance liquid-chromatography of dansyl derivatives with ultraviolet detection. J Chromatography 233:307–312

    Google Scholar 

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This work was supported by MPI 60% grant

Send offprint requests to F. Zambotti at the above address

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Zambotti, F., Zonta, N., Hafner, B. et al. Modification of GABA turnover in the striatum and hippocampus of the rat after zopiclone. Naunyn-Schmiedeberg's Arch Pharmacol 335, 547–550 (1987). https://doi.org/10.1007/BF00169122

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  • DOI: https://doi.org/10.1007/BF00169122

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