Role of nociceptin and opioid receptor like 1 on entrainment function in the rat suprachiasmatic nucleus

The suprachiasmatic nucleus of the hypothalamus is the master circadian clock in mammals. Phase shifts in circadian locomotor activity occur when an animal is exposed to light during the subjective night. An endogenous ligand of opioid receptor like 1, nociceptin is reported to inhibit light-induced phase shifts in locomotor activity rhythm. However, little is known about the role of opioid receptor like 1 receptors in the entrainment. Therefore, we investigated the involvement opioid receptor like 1 and its endogenous ligand, intnociceptin, in the suprachiasmatic nucleus and in the entrainment of circadian rhythms in rats. In an in vitro experiment, glutamate (1μM) -induced phase delay of suprachiasmatic nucleus neuronal activity rhythms was inhibited by nociceptin during the early subjective night. An opioid receptor like 1 antagonist, compound B (10μM), induced a phase delay, and this effect was blocked by nociceptin (10μM). Moreover, compound B (10μM) potentiated the glutamate (1μM) -induced phase delay. Fos expression in the suprachiasmatic nucleus of rats induced by photic stimulation (50 lux, 30 min) during the early subjective night was inhibited by treatment with nociceptin (0.5-10nM, i.c.v.). The effect of nociceptin (10nM, i.c.v.) was blocked by pretreatment with compound B (30mg/kg, i.p). In an in vivo experiment, nociceptin significantly inhibited a light-induced (300 lux, 1 h) phase delay of locomotor activity rhythms, and this effect was inhibited by Compound B. Compound B (30mg/kg, i.p.) significantly potentiated the light-induced phase delay. Nociceptin induced a neuronal firing phase advance (in vitro) and locomotor activity rhythms (in vivo) in the daytime and this effect was blocked by Compound B. These results suggest that opioid receptor like 1 receptors have an inhibitory effect at night, and a facilitative effect in the day, on phase changes.