Multiple controls exerted by 5-HT2C receptors upon basal ganglia function: From physiology to pathophysiology

P. De Deurwaerdère, M. Lagière, M. Bosc, S. Navailles
Exp Brain Res. 2013-04-25; 230(4): 477-511
DOI: 10.1007/s00221-013-3508-2

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Serotonin2C (5-HT2C) receptors are expressed in the basal ganglia, a group of
subcortical structures involved in the control of motor behaviour, mood and
cognition. These receptors are mediating the effects of 5-HT throughout different
brain areas via projections originating from midbrain raphe nuclei. A growing
interest has been focusing on the function of 5-HT2C receptors in the basal
ganglia because they may be involved in various diseases of basal ganglia
function notably those associated with chronic impairment of dopaminergic
transmission. 5-HT2C receptors act on numerous types of neurons in the basal
ganglia, including dopaminergic, GABAergic, glutamatergic or cholinergic cells.
Perhaps inherent to their peculiar molecular properties, the modality of controls
exerted by 5-HT2C receptors over these cell populations can be phasic, tonic
(dependent on the 5-HT tone) or constitutive (a spontaneous activity without the
presence of the ligand). These controls are functionally organized in the basal
ganglia: they are mainly localized in the input structures and preferentially
distributed in the limbic/associative territories of the basal ganglia. The
nature of these controls is modified in neuropsychiatric conditions such as
Parkinson’s disease, tardive dyskinesia or addiction. Most of the available data
indicate that the function of 5-HT2C receptor is enhanced in cases of chronic
alterations of dopamine neurotransmission. The review illustrates that 5-HT2C
receptors play a role in maintaining continuous controls over the basal ganglia
via multiple diverse actions. We will discuss their interest for treatments aimed
at ameliorating current pharmacotherapies in schizophrenia, Parkinson’s disease
or drugs abuse.


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