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- W4385463005 startingPage "106248" @default.
- W4385463005 abstract "Benzodiazepine (BZ) drugs treat seizures, anxiety, insomnia, and alcohol withdrawal by potentiating γ2 subunit containing GABA type A receptors (GABAARs). BZ clinical use is hampered by tolerance and withdrawal symptoms including heightened seizure susceptibility, panic, and sleep disturbances. Here, we investigated inhibitory GABAergic and excitatory glutamatergic plasticity in mice tolerant to benzodiazepine sedation. Repeated diazepam (DZP) treatment diminished sedative effects and decreased DZP potentiation of GABAAR synaptic currents without impacting overall synaptic inhibition. While DZP did not alter γ2-GABAAR subunit composition, there was a redistribution of extrasynaptic GABAARs to synapses, resulting in higher levels of synaptic BZ-insensitive α4-containing GABAARs and a concomitant reduction in tonic inhibition. Conversely, excitatory glutamatergic synaptic transmission was increased, and NMDAR subunits were upregulated at synaptic and total protein levels. Quantitative proteomics further revealed cortex neuroadaptations of key pro-excitatory mediators and synaptic plasticity pathways highlighted by Ca2+/calmodulin-dependent protein kinase II (CAMKII), MAPK, and PKC signaling. Thus, reduced inhibitory GABAergic tone and elevated glutamatergic neurotransmission contribute to disrupted excitation/inhibition balance and reduced BZ therapeutic power with benzodiazepine tolerance." @default.
- W4385463005 created "2023-08-02" @default.
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- W4385463005 date "2023-09-01" @default.
- W4385463005 modified "2023-10-18" @default.
- W4385463005 title "Inhibitory and excitatory synaptic neuroadaptations in the diazepam tolerant brain" @default.
- W4385463005 cites W1496861555 @default.
- W4385463005 cites W1516599165 @default.
- W4385463005 cites W1565551672 @default.
- W4385463005 cites W1647312149 @default.
- W4385463005 cites W1770729033 @default.
- W4385463005 cites W1788584426 @default.
- W4385463005 cites W1965899597 @default.
- W4385463005 cites W1967516237 @default.
- W4385463005 cites W1968107218 @default.
- W4385463005 cites W1969568645 @default.
- W4385463005 cites W1974574229 @default.
- W4385463005 cites W1978085895 @default.
- W4385463005 cites W1978423412 @default.
- W4385463005 cites W1978647461 @default.
- W4385463005 cites W1988489044 @default.
- W4385463005 cites W1990584558 @default.
- W4385463005 cites W1992374003 @default.
- W4385463005 cites W2001173861 @default.
- W4385463005 cites W2001619275 @default.
- W4385463005 cites W2013683917 @default.
- W4385463005 cites W2017583361 @default.
- W4385463005 cites W2018494226 @default.
- W4385463005 cites W2019100774 @default.
- W4385463005 cites W2024380057 @default.
- W4385463005 cites W2025698938 @default.
- W4385463005 cites W2029215893 @default.
- W4385463005 cites W2029854919 @default.
- W4385463005 cites W2031990844 @default.
- W4385463005 cites W2035530017 @default.
- W4385463005 cites W2036463020 @default.
- W4385463005 cites W2036809519 @default.
- W4385463005 cites W2038457835 @default.
- W4385463005 cites W2038477005 @default.
- W4385463005 cites W2038728741 @default.
- W4385463005 cites W2041124713 @default.
- W4385463005 cites W2050601812 @default.
- W4385463005 cites W2054289440 @default.
- W4385463005 cites W2059932334 @default.
- W4385463005 cites W2061648961 @default.
- W4385463005 cites W2066114516 @default.
- W4385463005 cites W2068781003 @default.
- W4385463005 cites W2071614169 @default.
- W4385463005 cites W2071646230 @default.
- W4385463005 cites W2076762938 @default.
- W4385463005 cites W2080552659 @default.
- W4385463005 cites W2083623577 @default.
- W4385463005 cites W2091486815 @default.
- W4385463005 cites W2108694451 @default.
- W4385463005 cites W2112674553 @default.
- W4385463005 cites W2119109339 @default.
- W4385463005 cites W2119677026 @default.
- W4385463005 cites W2119914706 @default.
- W4385463005 cites W2127623068 @default.
- W4385463005 cites W2137471600 @default.
- W4385463005 cites W2142169831 @default.
- W4385463005 cites W2154223842 @default.
- W4385463005 cites W2160630552 @default.
- W4385463005 cites W2161006430 @default.
- W4385463005 cites W2167092596 @default.
- W4385463005 cites W2169905651 @default.
- W4385463005 cites W2273924248 @default.
- W4385463005 cites W2281412879 @default.
- W4385463005 cites W2400519656 @default.
- W4385463005 cites W2418677768 @default.
- W4385463005 cites W2804368056 @default.
- W4385463005 cites W2903074009 @default.
- W4385463005 cites W2903124740 @default.
- W4385463005 cites W2907708451 @default.
- W4385463005 cites W2912316467 @default.
- W4385463005 cites W2947763854 @default.
- W4385463005 cites W2952160703 @default.
- W4385463005 cites W2971463570 @default.
- W4385463005 cites W3014677086 @default.
- W4385463005 cites W3038758511 @default.
- W4385463005 cites W3214054678 @default.
- W4385463005 cites W4220692518 @default.
- W4385463005 cites W4238945726 @default.
- W4385463005 cites W4300166879 @default.
- W4385463005 cites W775019103 @default.