Orexin is a member of neuropeptides which is involved in the central motor control. The substantia nigra pars compacta (SNc) is an important nucleus participating in motor control under both physiological and pathological conditions. Morphological studies reveal that orexinergic neurons located in lateral hypothalamus innervate the SNc. Both orexin-1 receptors (OX₁ R) and orexin-2 receptors (OX₂ R) are expressed in the SNc. To investigate the effects of orexins on SNc, single unit in vivo extracellular recordings and behavioral tests were performed in this study. Micro-pressure administration of orexin A and orexin B significantly increased the spontaneous firing rate of nigral DAergic neurons by 65.87 ± 7.73% and 90.49 ± 17.83%, respectively. The excitatory effects of orexin A on nigral DAergic neurons were mainly mediated by OX₁ R, while OX₂ R were involved in the increase in firing rate induced by orexin B. Selectively blocking OX₁ R and OX₂ R significantly decreased the firing rate of nigral DAergic neurons by 36.77 ± 6.26% and 32.04 ± 6.12%, respectively, which suggested that endogenous orexins modulated the spontaneous firing activity of nigral DAergic neurons. Finally, both elevated body swing test and haloperidol-induced postural behavioral test showed that unilateral microinjection of orexin A and orexin B induced significantly contralateral-biased swing and deflection behavior. Meanwhile, the specific OX₁ R and OX₂ R antagonists produced opposite effects. The present electrophysiological and behavioral studies suggested that orexins increased the firing activity of nigral DAergic neurons and participated in central motor control. Open Practices Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.

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