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• W2118767317 abstract "Modulation of GABA function following 1 week oral administration of flurazepam (FZP) was investigated in chloride-loaded, rat hippocampal CA1 pyramidal neurons. Rats were sacrificed 2 or 7 days after ending drug treatment, when anticonvulsant tolerance was present or absent in vivo, respectively. Spontaneous (s)IPSCs and miniature (m)IPSCs were recorded using whole-cell voltage-clamp techniques. s/mIPSCs were bicuculline-sensitive, voltage-dependent, and reversed their polarity at 0 mV, the predicted ECl-. Comparisons of s/mIPSCs between FZP-treated and control groups were made at Vh = -90, -70, and -50 mV. The frequency of sIPSCs, but not mIPSCs, was significantly decreased in FZP-treated neurons 2 days, but not 7 days, after FZP treatment, suggesting a decrease in interneuron activity. These conclusions were supported by the negative findings of additional studies of [3H]GABA release from hippocampal slices and [3H]GABA uptake from hippocampal synaptosomes. The lack of change in the paired-pulse depression of GABAB-mediated IPSPs suggested that autoreceptor function was also not impaired following chronic FZP treatment. A large reduction in both sIPSC and mIPSC amplitude (60%) in FZP-treated neurons, the absence of mIPSCs in one-third of FZP-treated cells, and a measurable reduction in synaptic and unitary conductance confirmed that postsynaptic GABAA receptor function was profoundly impaired in FZP-treated CA1 neurons. Zolpidem, an α1-selective benzodiazepine receptor ligand, enhanced mIPSC amplitude and decay, but its ability to prolong mIPSC decay was reduced in FZP-treated neurons. Several pre- and postsynaptic changes at GABAergic synapses on CA1 pyramidal cells might be related to the decreased tonic GABA inhibition in FZP-treated CA1 neurons associated with the expression of benzodiazepine anticonvulsant tolerance. Synapse 31:263–277, 1999. © 1999 Wiley-Liss, Inc." @default.
• W2118767317 created "2016-06-24" @default.
• W2118767317 creator A5066965969 @default.
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• W2118767317 date "1999-03-15" @default.
• W2118767317 modified "2023-09-25" @default.
• W2118767317 title "Benzodiazepine tolerance at GABAergic synapses on hippocampal CA1 pyramidal cells" @default.
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• W2118767317 doi "https://doi.org/10.1002/(sici)1098-2396(19990315)31:4<263::aid-syn4>3.0.co;2-j" @default.
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• W2118767317 hasPublicationYear "1999" @default.
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