Antagonist-Induced Reversal of Functional and Structural Measures of Hippocampal Benzodiazepine Tolerance

Effects of FLM injection (4 mg/kg i.p.) on tolerance to zolpidem's ability to prolong mIPSC decay in CA1 neurons recorded in in vitro rat hippocampal slices 2 days after ending 1-week FZP treatment. A, representative traces of the decay phase of averaged mIPSCs, before and after superfusion of 1 μM zolpidem. CA1 neurons were recorded from control (CON) and FZP-treated rats injected with vehicle or FLM 24 h before recording. The peak amplitude of averaged mIPSCs from an FZP-treated neuron was normalized to the peak amplitude of control averaged mIPSCs for comparison. B, effects of 1 μM zolpidem to prolong mIPSC decay in CA1 neurons was expressed as a percentage of the baseline average mIPSC decay recorded in the absence of zolpidem. Zolpidem tolerance was measured as a significant reduction in the ability of zolpidem to enhance mIPSC decay in FZP-VEH neurons (n = 6) in comparison to CON-VEH neurons (n = 7). There was no significant difference in zolpidem's ability to prolong decay between neurons from FZP-treated (n = 6) and control (n = 7) rats injected with FLM 24 h before recording, as shown in Table1.