l‐Dopa activates histaminergic neurons

Non-technical summary  L-Dopa is an effective medication for Parkinson's disease (PD), but loses efficiency with time. This can be delayed by treatment with histamine antagonists. We show histaminergic neurons in the hypothalamus controlling wakefulness are excited by L-Dopa, which they can take up and transform to dopamine. They innervate the whole brain, in particular the striatum which is deficient of dopamine in PD. We revealed mechanisms of excitation of histaminergic neurons by L-Dopa and dopamine opening new avenues for the treatment of PD and sleep disorders.