The effects of benzodiazepines on orexinergic systems in rat cerebrocortical slices.

He, Ying; Kudo, Mihoko; Kudo, Tsuyoshi; Kushikata, Tetsuya; Li, Enyou; Hirota, Kazuyoshi · Anesth Analg · 2007

basic_science · Level V

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Abstract

As orexinergic (OXergic) neurons have been reported to mediate emotional changes, benzodiazepines might interact with OXergic neurons. 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. 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 microM, P < 0.01), which was insensitive to flumazenil, was significantly lower than that of diazepam and flunitrazepam (around 60 microM), whereas the IC50s for K+-evoked release were not different among the benzodiazepines. There may be no interaction between OXergic neurons and central benzodiazepine receptors.

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