Histamine H₃ receptors and their role in basal ganglia physiology and pathophysiology

Through interaction with G protein-coupled receptors, histamine regulates pre- and post-synaptically a number of brain functions such as wakefulness, locomotor activity, autonomic and vestibular functions, feeding, drinking, analgesia and memory. Four such receptors have been cloned to date, and three of them (H₁, H₂, and H₃) are widely distributed in the central nervous system, which contains the great majority of histamine H₃ receptors (H₃Rs). These receptors are expressed at high densities in the basal ganglia, a group of subcortical neuronal nuclei intimately involved in the regulation of posture and movement. In this review the main characteristics of H₃Rs (structure, isoforms, constitutive activity and signaling) are briefly described, to then summarize our own work regarding the H₃R-mediated regulation of synaptic transmission in the basal ganglia. Finally, the possible participation of H₃Rs in the pathophysiology of Parkinson's disease is discussed. Based on the information herein reviewed it is concluded that H₃Rs play a relevant role in basal ganglia function both in normal and pathological conditions, and that H₃R agonists and antagonists may have potential use in the treatment of both Parkinson's disease and the complications of the current pharmacological therapies of the disorder.