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

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