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ANESTHETIC PHARMACOLOGY

The Effects of Benzodiazepines on Orexinergic Systems in Rat Cerebrocortical Slices

Ying He, MD^*, Mihoko Kudo, PhD^*, Tsuyoshi Kudo, PhD^*, Tetsuya Kushikata, MD^*, Enyou Li, MD, and Kazuyoshi Hirota, MD, FRCA^*

From the *Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Japan; and Department of Anesthesiology, First Clinical College of Harbin Medical University, Harbin, China.

Address correspondence and reprint requests to K. Hirota, Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki 036-8562, Japan. Address e-mail to hirotak{at}cc.hirosaki-u.ac.jp.

BACKGROUND: As orexinergic (OXergic) neurons have been reported to mediate emotional changes, benzodiazepines might interact with OXergic neurons.

METHODS: We examined the interactions between OXergic neurons and benzodiazepine receptors in orexin-A (100 nM) and K⁺ (25 mM)-evoked norepinephrine release from rat cerebrocortical slices.

RESULTS: Midazolam, diazepam, and flunitrazepam concentration-dependently inhibited both OX-A- and K⁺-evoked norepinephrine release. The IC₅₀ of midazolam for orexin-A-evoked release (0.87 µM, P < 0.01), which was insensitive to flumazenil, was significantly lower than that of diazepam and flunitrazepam (around 60 µM), whereas the IC₅₀s for K⁺-evoked release were not different among the benzodiazepines.

CONCLUSION: There may be no interaction between OXergic neurons and central benzodiazepine receptors.

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