Role of central 5-HT2C receptor in the control of basal ganglia functions

Abstract

The basal ganglia are a highly interconnected group of subcortical nuclei in the vertebrate brain that play a critical role not only in the control of movements but also in some cognitive and behavioural functions. Several recent studies have emphasized that serotonergic pathways in the central nervous system (CNS) are intimately involved in the modulation of the basal ganglia and in the pathophysiology of human involuntary movement disorders. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of the basal ganglia. In fact, serotonergic terminals have been reported to make synaptic contacts with both dopamine (DA)-containing neurons and γ-aminobutyric acid (GABA)-containing neurons in the striatum, globus pallidus, subthalamus and substantia nigra. These brain areas contain the highest concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. Furthermore, in these structures a high expression of 5-HT different receptor subtypes has been revealed. In this paper, evidence demonstrating the serotonergic control of basal ganglia functions will be reviewed, focusing on the role of the 5-HT2C receptor subtype. Moreover, the involvement of 5-HT2C receptors in neurological disorders such as Parkinson’s diseases and other related motor disorders, and their management with drugs acting on 5-HT2C receptor will be discussed.