Opposite modulation of histaminergic neurons by nociceptin and morphine

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.