Central orexinergic system, which originates solely from the hypothalamus but projects almost the whole brain, has been traditionally implicated in regulation of many nonsomatic basic functions, such as sleep/wake cycle, feeding behavior, emotion, pain, and addiction.Nevertheless, its functions on motor control are seldom investigated.Interestingly, our previous studies have revealed an excitatory effect of orexin on neurons in the cerebellar interpositus nucleus (IN), one of the final outputs of spinocerebellum coordinating body and limb movements, in adult rats.Thus, in the present study, receptor mechanism underlying the orexin-induced excitation on cerebellar IN neurons in rats, particularly at three key stages of development of cerebellar circuitry (7-14 days, 21-28 days, and adult), were investigated.First, real-time RT-PCR results showed that both orexin 1 receptors (OX1Rs) and orexin 2 receptors (OX2Rs) are existed in the rat IN at all three different ages.Next, by using brain slice preparations and extracellular recordings, effect of orexin and orexinergic agents on IN neurons were observed.The results showed that orexin-A (300 nM) excited the IN neurons at all three developmental stages (n =29, 24, and 33, respectively).Moreover, the orexin-induced excitation on IN neurons was not only partly blocked by selective OX1R antagonist SB334867 (1, 3, 10 μM) in a dose-dependent manner, but also dose-dependently mimicked by selective OX2R agonist [Ala11, D-Leu15]-orexin-B (300 nM and 1 μM) at all three ages (n =9, 10, 8; and n =15, 13, 14, respectively), indicating that both OX1R and OX2R mediate the orexin-induced excitation on IN neurons which does not change with age.Furthermore, both the increase of excitatory response elicited by orexin-A or [Ala11, D-Leu15]-orexin-B and the antagonistic effect induced by SB334867 on IN neurons did not change along with development, although the basic spontaneous firing rate of IN neurons increases with age.All these results demonstrate a consistent excitatory effect oforexin on IN neurons with the unchanged underlying receptor mechanism in rats at different development stages, and suggest that central orexinergic system may play an important and substantial role in cerebellar motor control.