Sleep and wakefulness are under control of brain for sustainability of brain functions. However the cellular and systems-level mechanisms underlying the regulation of sleep-wake are still unclear. Noradrenergic (NA) neurons, located in the pontine locus coeruleus (LC), play pivotal roles in generating and sustaining the state of wakefulness and REM sleep. Orexin neurons, located in the lateral hypothalamus, are involved in the promotion and maintenance of wakefulness. It is thought that there is a functional interaction between orexin and NA systems. In fact, orexin excite NA neurons in the LC through orexin type-1 receptors (OX1Rs). On the other hand, recent histological study has shown that orexin type-2 receptors (OX2Rs) are expressed not in NA neurons but in GABAergic neurons in the LC. To investigate whether OX2Rs in the LC have a function in the interaction between orexin and NA systems, we performed patch-clamp recordings and immunohistochemistry on the LC. Application of orexin B, which activate OX2Rs but not OX1Rs, reduced spontaneous firing of NA neurons. The reduction was not observed in the presence of the GABAAR antagonists. Orexin neuron varicosities were found in close proximity to GABAergic neurons in the LC. Orexin B increased firing rates of the GABAergic neurons. These results suggest that orexin neurons provide NA neurons not only with direct excitation via OX1Rs on NA neurons but also with indirect inhibition via OX2Rs on local GABAergic neurons in the LC, thereby contributing to feed forward inhibition of NA neurons to prevent them from hyperactivation.