The Interaction of Histamine H 3 and Dopamine D 1 Receptors on Hyperkinetic Alterations in Animal Models of Parkinson's Disease

Parkinson's disease is associated with the loss of more than 40% of dopaminergic neurons in the substantia nigra pars compacta. One of the therapeutic options for restoring striatal dopamine levels is the administration of L-3,4-dihydroxyphenylalanine (L-Dopa). However, Parkinson's disease patients on long-term L-Dopa therapy often experience motor complications, such as dyskinesias. L-Dopa-induced dyskinesias (LIDs) manifest as abnormal involuntary movements and are produced by elevated striatal dopamine levels, which lead to increased activity of the basal ganglia direct striato-nigral pathway. Dopamine D receptors are more than 95% confined to neurons of the direct pathway, where they colocalize with histamine H receptors. There is evidence of functional interactions between D and H receptors, and here we review the consequences of these interactions on LIDs.