Bumetanide prevents diazepam-modified anxiety-like behavior in lipopolysaccharide-treated mice

Benzodiazepine receptor agonists are widely prescribed therapeutic agents that alter gamma-aminobutyric acid (GABA)A activity and have anxiolytic effects. Post-operative use of benzodiazepines is a risk factor delirium. Inflammatory conditions the effects benzodiazepine. We investigated effect diazepam, typical benzodiazepine anxiolytic, on changes in emotional behavior mice hole-board test after lipopolysaccharide (LPS) treatment. Diazepam dose-dependently increased number head-dips at doses did not locomotor activity; however, diazepam significantly decreased LPS-treated mice. Flumazenil, antagonist, normalized decrease head-dipping caused by treatment normal The was attenuated minocycline further found blocked bumetanide, Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) These findings suggest induces anxiety-like under inflammation conditions, may cause GABAA dysfunction associated with chloride plasticity mediated NKCC1, which contributes to benzodiazepine-induced delirium surgery.