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. 2019 Jan 9;9:1523. doi: 10.3389/fphar.2018.01523

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Copyright © 2019 Neumann, Rudolph, Knutson, Li, Cook, Hentschke, Antkowiak and Drexler.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Effects of zolpidem in the additional presence of the benzodiazepine antagonist flumazenil. (A) Action of zolpidem (0.75 μM) in the absence and presence of flumazenil (0.75 μM) given as boxplot. While depression of high neuronal activity (0 – 50 ms after initiation of up state) by zolpidem is evident (left side, n = 30, median = 0.86, iqr = 0.33 of normalized activity) it is absent in the additional presence of flumazenil (right side, n = 47, median = 1.02, iqr = 0.29 of normalized activity, p = 0.0147, Mann–Whitney U-test). (B) Action of zolpidem (0.75 μM) in the presence of flumazenil (0.75 μM) given as PETH, with the dark blue curve showing the neuronal activity in the sole presence of flumazenil and the light blue curve showing a combined application of flumazenil and zolpidem. Within the first 100 ms after the beginning of neuronal up states the depressant action of zolpidem is absent in the additional presence of flumazenil.