Reduction of fear-potentiated startle by benzodiazepines in C57BL/6J mice

苯二氮卓类药物可减少 C57BL/6J 小鼠因恐惧而增强的惊吓

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作者:Kiersten S Smith, Edward G Meloni, Karyn M Myers, Ashlee Van't Veer, William A Carlezon Jr, Uwe Rudolph

Conclusions

We used a modified and pharmacologically-validated paradigm to assess FPS in mice thereby providing a powerful tool to examine the neurobiology of PTSD in genetic models of anxiety generated on the C57BL/6J background.

Methods

We modified several FPS experimental parameters and developed a paradigm to assess conditioned fear in C57BL/6J mice. The 6-day protocol consisted of three startle Acclimation days, a Pre-Test day followed by Training and Testing for FPS. Subject responses to the effects of three benzodiazepines were also examined.

Results

C57BL/6J mice had low levels of unconditioned fear assessed during Pre-Test (15-18%) but showed robust FPS (80-120%) during the Test session. Conditioned fear responses extinguished over repeated test sessions. Administration of the benzodiazepines alprazolam (0.5 and 1 mg/kg, i.p.), chlordiazepoxide (5 and 10 mg/kg, i.p.), and diazepam (1, 2, and 4 mg/kg, i.p.) significantly reduced FPS to Pre-Test levels. Conclusions: We used a modified and pharmacologically-validated paradigm to assess FPS in mice thereby providing a powerful tool to examine the neurobiology of PTSD in genetic models of anxiety generated on the C57BL/6J background.

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