(A) Mice were randomly allocated to 10 groups (n=15/group) and were pre-treated intraperitoneally (ip) with antagonists (yohimbine/atipamezole/methyllycaconitine). Thirty minutes later mice were trained in the trace-fear conditioning paradigm. After the training session, high mobility group box 1 protein (HMGB1) or vehicle (phosphate-buffered saline) was administered ip dexmedetomidine was administered every 2 hours × 3 times. 72 hours after HMGB1, testing was performed in the trace-fear conditioning.
(B) Mice were randomly allocated to 10 groups (n=8/group) and were pre-treated ip with antagonists (yohimbine/atipamezole/methyllycaconitine) and 30 minutes later HMGB1 was administered. Dexmedetomidine was administered every 2 hours × 3 times. Blood and tissue were collected 24 hours later.
(C) Mice were randomly allocated to three groups (n=15/group): control (vehicle only); surgery/anesthesia and surgery/anesthesia + dexmedetomidine. Mice were trained in the trace fear-conditioning paradigm. After the training session, animals were anesthetized with isoflurane and subjected to aseptic trauma. Dexmedetomidine was administered and the mice were tested in the trace-fear conditioning 3 days later.
(D) Mice were randomly allocated to 3 groups (n=5–6/group): control (vehicle only); surgery/anesthesia and surgery/anesthesia + dexmedetomidine. Mice were anesthetized with isoflurane and subjected to aseptic trauma. Dexmedetomidine was administered and blood and tissue were collected 24 hours later.