Morphine Inhibits Sleep-Promoting Neurons in the Ventrolateral Preoptic Area Via Mu Receptors and Induces Wakefulness in Rats

摘要: Morphine is the most efficacious and widely prescribed treatment for pain. However, it decreases total amount of deep sleep rapid eye movement in humans. Acute morphine administration at low doses causes wakefulness animal models. To clarify mechanism by which affects sleep–wake behavior, we investigated effects on sleep-promoting neurons ventrolateral preoptic area (VLPO), a putative sleep-active nucleus, using vitro brain slices patch-clamp technique. We also examined profiles after opioid receptor antagonist to VLPO EEG electromyogram recordings freely moving rats. The results showed that inhibited firing rate hyperpolarized their membrane potentials without affecting interneurons VLPO. Morphine-induced hyperpolarization could be reversed by, D-Phe-Cys-Thr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), mu antagonist, presence tetrodotoxin. receptors were blocked CTOP, still suppressed neurons. This effect was antagonized nor-BIN, kappa antagonist. Activation U50488H These indicate inhibit activity through receptors. revealed injected subcutaneously induced arousal dose-dependent manner. CTOP microinjected into morphine, but nor-BIN did not. alone not associated with any changes physiological cycle. Taken together, these findings clearly inhibits so induces