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.


CONCLUSIONS
There may be no interaction between OXergic neurons and central benzodiazepine receptors.
He
Ying
Y
Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Japan.
Kudo
Mihoko
M
Kudo
Tsuyoshi
T
Kushikata
Tetsuya
T
Li
Enyou
E
Hirota
Kazuyoshi
K
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D008874:Midazolam; D009638:Norepinephrine