The role of dopamine in sleep-wake regulation is unclear, despite the fact that psychostimulants cause behavioural arousal. We investigated the interaction of dopamine with the wake-promoting histaminergic system. Immunocytochemistry revealed localization of tyrosine hydroxylase-positive cell bodies (dopaminergic neurons) and fibres in close proximity to the histaminergic neurons in the dorsolateral tuberomamillary nucleus (TMN) neighbouring the substantia nigra. Double stainings revealed D2 or D1 receptors in many glial cells and fibroblasts but not on TMN neurons in slices as well as primary cultures. The firing rate of pharmacologically identified TMN neurons in rat hypothalamic slices was enhanced by quinpirole (100mM). This activation was abolished by sulpiride (10mM). Participation of nitric oxide, glutamate, ATP and growth factors, which could be responsible for the neuronal excitation through D1/D2 receptor activation of non-neuronal elements (glia or fibroblasts) was excluded as a major mechanism. Calcium imaging with fluo4 performed in primary cultures containing TMN neurons in the presence of TTX revealed an immediate calcium rise in some neurons upon perfusion of quinpirole followed by a delayed (5 min) induction of calcium oscillations in some non-neuronal cells which decayed within 10-30 min. We conclude that quinpirole directly excites TMN neurons through D2-like receptors.