Loss of zolpidem efficacy in the hippocampus of mice with the GABAAreceptor γ2 F77I point mutation
| Autor: | Elli Leppä, Peer Wulff, Waltraud Ogris, Marco Capogna, Peter Somogyi, H. Hoeger, Esa R. Korpi, Anni-Maija Linden, William Wisden, Werner Sieghart, A. Oberto, C. Halbsguth, Theofanis Karayannis, D. W. Cope, Francesco Ferraguti |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Drug Resistance/genetics Pyridines Drug Resistance Action Potentials Pharmacology Action Potentials/drug effects Hippocampus Synaptic Transmission Mice Radioligand Assay chemistry.chemical_compound 0302 clinical medicine Receptor Pyridines/pharmacology 0303 health sciences GABAA receptor Chemistry Pyramidal Cells musculoskeletal neural and ocular physiology General Neuroscience Receptors GABA-A/drug effects Female Flunitrazepam psychological phenomena and processes medicine.drug Agonist Zolpidem medicine.drug_class Synaptic Transmission/drug effects Cholinergic Agonists Inhibitory postsynaptic potential Binding Competitive Neural Inhibition/drug effects Mice Neurologic Mutants 03 medical and health sciences Interneurons medicine Point Mutation Animals Carbachol/pharmacology Hippocampus/drug effects Pyramidal Cells/drug effects GABA Agonists GABA Agonists/pharmacology 030304 developmental biology Benzodiazepine Interneurons/drug effects Neural Inhibition Point Mutation/drug effects Binding Competitive/drug effects Receptors GABA-A Cholinergic Agonists/pharmacology Mice Inbred C57BL nervous system Muscimol Carbachol 030217 neurology & neurosurgery |
| Zdroj: | Cope, D W, Halbsguth, C, Karayannis, T, Wulff, P, Ferraguti, F, Hoeger, H, Leppä, E, Linden, A-M, Oberto, A, Ogris, W, Korpi, E R, Sieghart, W, Somogyi, P, Wisden, W & Capogna, M 2005, ' Loss of zolpidem efficacy in the hippocampus of mice with the GABAA receptor gamma2 F77I point mutation ', The European journal of neuroscience, vol. 21, no. 11, pp. 3002-16 . https://doi.org/10.1111/j.1460-9568.2005.04127.x Europe PubMed Central |
| ISSN: | 1460-9568 0953-816X |
| DOI: | 10.1111/j.1460-9568.2005.04127.x |
| Popis: | Zolpidem is a hypnotic benzodiazepine site agonist with some gamma-aminobutyric acid (GABA)(A) receptor subtype selectivity. Here, we have tested the effects of zolpidem on the hippocampus of gamma2 subunit (gamma2F77I) point mutant mice. Analysis of forebrain GABA(A) receptor expression with immunocytochemistry, quantitative [(3)H]muscimol and [(35)S] t-butylbicyclophosphorothionate (TBPS) autoradiography, membrane binding with [(3)H]flunitrazepam and [(3)H]muscimol, and comparison of miniature inhibitory postsynaptic current (mIPSC) parameters did not reveal any differences between homozygous gamma2I77/I77 and gamma2F77/F77 mice. However, quantitative immunoblot analysis of gamma2I77/I77 hippocampi showed some increased levels of gamma2, alpha1, alpha4 and delta subunits, suggesting that differences between strains may exist in unassembled subunit levels, but not in assembled receptors. Zolpidem (1 microm) enhanced the decay of mIPSCs in CA1 pyramidal cells of control (C57BL/6J, gamma2F77/F77) mice by approximately 60%, and peak amplitude by approximately 20% at 33-34 degrees C in vitro. The actions of zolpidem (100 nm or 1 microm) were substantially reduced in gamma2I77/I77 mice, although residual effects included a 9% increase in decay and 5% decrease in peak amplitude. Similar results were observed in CA1 stratum oriens/alveus interneurons. At network level, the effect of zolpidem (10 microm) on carbachol-induced oscillations in the CA3 area of gamma2I77/I77 mice was significantly different compared with controls. Thus, the gamma2F77I point mutation virtually abolished the actions of zolpidem on GABA(A) receptors in the hippocampus. However, some residual effects of zolpidem may involve receptors that do not contain the gamma2 subunit. |
| Databáze: | OpenAIRE |
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