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Glutamate and benzodiazepine receptor autoradiography in rat brain after repetition of alcohol dependence

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Abstract

During repeated alcohol withdrawal, convulsive withdrawal behaviour has been shown to be increased in a kindling-like manner in both clinical and experimental studies. In the present experiment, quantitative autoradiography was used to investigate binding of tritiated ligands to glutamate receptor subtypes and the benzodiazepine/GABA (BZ/GABA) receptor complex in rats exposed to 14 episodes of alcohol withdrawal. Seizures were detected in 25% of the animals during withdrawal episode 10–13. Repeated alcohol withdrawal resulted in a decrease in the number of [3H]-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]-AMPA) binding sites in striatum and subregions of the entorhinal cortex, the cerebellum and the hippocampus, while the [3H]-flunitrazepam binding was down-regulated in the frontal cortex. There was no differences between the controls and the multiple withdrawal animals regarding the [3H]-dizocilpine ([3H]-MK801) binding and the [3H]-kainic acid binding. However, within the latter group, those animals in which withdrawal seizures were observed had increased [3H]-MK801 binding sites in focal regions of entorhinal cortex and hippocampus, compared to those in which seizures were not observed. The decreased AMPA binding suggested impaired glutamate neurotransmission. As such, this receptor probably did not contribute to alcohol withdrawal kindling, but rather was involved in seizure protective mechanisms during this process.

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Authors and Affiliations

  1. Neuropsychiatric Research Group, Department of Psychiatry O-6234, Rigshospitalet, Belgdamsvej 9, DK-2100, Copenhagen, Denmark

    J. Ulrichsen & B. Bech

  2. Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark

    B. Ebert

  3. Molecular Neurophathology Laboratory, Institute of Neuropathology, University of Copenhagen, Frederik V's vej 11, 6, DK-2100, Copenhagen, Denmark

    N. H. Diemer

  4. The Danish National Institute for Educational Research, Hermodsgade 28, DK-2200, Copenhagen, Denmark

    P. Allerup

  5. Department of Psychiatry, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400, Copenhagen NV, Denmark

    R. Hemmingsen

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  1. J. Ulrichsen
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  4. N. H. Diemer
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  6. R. Hemmingsen
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Ulrichsen, J., Bech, B., Ebert, B. et al. Glutamate and benzodiazepine receptor autoradiography in rat brain after repetition of alcohol dependence. Psychopharmacology 126, 31–41 (1996). https://doi.org/10.1007/BF02246408

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  • DOI: https://doi.org/10.1007/BF02246408

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