Title: Both Type 1 and Type 2 Receptors Transmit the Behavioral Effects of Orexin/Hypocretin
Abstract: Two receptors have been identified for orexin (hypocretin). The Type 1 receptor (OX1R) binds orexin A preferentially, while the type 2 receptor (OX2R) binds both orexin A and orexin B with apparently equally affinity. In addition a role in the physiologic regulation of sleep/wakefulness, orexin influences arousal state. We examined the receptor subtype that mediates the effect of orexin A on spontaneous locomotor activity (SLA) in male rats. Orexin A stimulated dose related increases in all aspects of SLA examined in the Opto-Max Activity monitor. These effects were only partially blocked by the selective OX1R antagonist SB- 408124, with the exception of the actions on rearing activity and vertical stereotypy which were completely prevented by pretreatment with the antagonist. The failure of the antagonist to completely prevent the action of orexin A on most aspects of SLA may be due to an action on the OX2R. The selective OX2R agonist [(Ala11, Leu15)-orexin B] also significantly stimulated SLA, and those effects were not compromised by pretreatment with the OX1R antagonist. Thus orexin A stimulates arousal state by actions on both the type 1 and type 2 receptors. (Supported by NIH HL68652)