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Updated: Jun 8, 2026
Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat
Published on: September 12, 2014
Reduction of fear-potentiated startle by benzodiazepines in C57BL/6J mice
Kiersten S Smith1, Edward G Meloni, Karyn M Myers
1Department of Psychiatry, McLean Hospital and Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. ksmith@mclean.harvard.edu
Rationale:
Anxiety disorders affect 18% of the United States adult population annually. Recent surges in the diagnosis of posttraumatic stress disorder (PTSD) from combat-exposed veterans have prompted an urgent need to understand the pathophysiology underlying this debilitating condition.
Objectives:
Anxiety and fear responses are partly modulated by gamma aminobutyric acid type A (GABA(A)) receptor-mediated synaptic inhibition; benzodiazepines potentiate GABAergic inhibition and are effective anxiolytics. Many genetically modified mouse lines are generated and/or maintained on the C57BL/6J background, a strain where manipulation of anxiety-like behavior using benzodiazepines is difficult. Fear-potentiated startle (FPS), a test of conditioned fear, is a useful preclinical tool to study PTSD-like responses but has been difficult to establish in C57BL/6J mice.
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.
