We have studied the effects of nociceptin/orphanin FQ on the histaminergic
neurons in the tuberomammillary (TM) nucleus and compared them with the act
ions of opioid agonists. Intracellular recordings of the membrane potential
were made with sharp electrodes from superfused rat hypothalamic slices. N
ociceptin strongly inhibited the firing of the TM neurons. In the concentra
tion range 10-300 nM, nociceptin hyperpolarized the neurons in a dose-depen
dent and reversible manner. Insensitivity to tetrodotoxin indicated a posts
ynaptic effect which was associated with decreased input resistance. Voltag
e-current plots suggested the involvement of a potassium conductance which
was highly sensitive to Ba2+ and decreased by Cs+, in keeping with the acti
vation of an inwardly rectifying potassium channel. Morphine (20-100 mu M)
depolarized the TM neurons and increased their firing, and this effect was
blocked by tetrodotoxin. Dynorphin A(1-13) at 100-300 nM did not affect the
TM neurons. Nociceptin and morphine modulate the activity of the TM neuron
s, and most likely histamine release, in opposite ways. Histamine has an an
tinociceptive effect in the brain and may be involved in opioid-induced ana
lgesia. Nociceptin might therefore influence pain transmission by inhibitin
g opioid-induced histamine release from the TM nucleus and also modulate ot
her physiological mechanisms which have been ascribed to the histaminergic
system. (C) 2000 Elsevier Science Ltd. All rights reserved.