Abstract
The orexin system regulates various functions, including sleep/wake cycles, feeding, and cognition. Orexin A and orexin B are endogenous neuropeptides for both orexin 1 (OX1) and orexin 2 (OX2) receptors. Orexin A has a potent agonistic activity for both the receptors and is known to increase locomotor activity in rats. However, it has not been elucidated how each receptor contributes to orexin A-induced hyperlocomotion. We examined the effects of an OX1 receptor antagonist, SB 334867, and an OX2 receptor antagonist, EMPA, as well as an OX1 and OX2 receptor antagonist on hyperlocomotion caused by intracerebroventricular administration of orexin A or an OX2 receptor agonist, ADL-OXB ([Ala11,d-Leu15]-orexin B), in rats. EMPA (100 mg/kg, ip) but not SB 334867 (3-10 mg/kg, ip) showed antagonistic effects on ADL-OXB-induced hyperlocomotion without affecting the spontaneous locomotor activity. Both EMPA (100 mg/kg, ip) and the OX1 and OX2 receptor antagonist (3-30 mg/kg, po) antagonized orexin A-induced hyperlocomotion, while SB 334867 (3‒-10 mg/kg, ip) showed no effects. Our results suggest that orexin A-induced hyperlocomotion is mainly mediated by the activation of the OX2 receptor.
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