Experimental Brain Research

, Volume 230, Issue 4, pp 477–511 | Cite as

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

  • P. De DeurwaerdèreEmail author
  • M. Lagière
  • M. Bosc
  • S. Navailles


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.


Serotonin 2C receptor Basal ganglia Dopamine Motor control Parkinson Dyskinesia Addiction 


5-HT2C receptor

Serotonin2C receptor




Dorsal raphe nucleus


Medial raphe nucleus










Central nervous system


High-frequency stimulation


Nucleus accumbens


Subthalamic nucleus


Entopeduncular nucleus


Internal globus pallidus


External globus pallidus


Substantia nigra pars compacta


Substantia nigra pars reticulata


Ventral tegmental area


Orbitofrontal cortex


Medial prefrontal cortex















Ro 60-0175




SB 228357


SB 206553




SB 242084

6-Chloro-5-methyl-1-[6-(2-methylpiridin-3-yloxy)pyridine-3-yl carbamoyl] indoline

SB 243213



(+)-cis 4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo[1,7-bc][2,6]-naphthyridine


N-{5-[5-(2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)pentanoyl] -2,4-dimethoxyphenyl}-4-(trifluoromethyl)benzenesulfonamide


(6-Chloro-5-methyl-1-(5-quinolylcarbamoyl) indoline



SB 200646

N-(1-methyl-5-indolyl)-N′-(3-pyridyl) urea


Glutamic acid decarboxylase


Tyrosine hydroxylase


Reverse transcription polymerase chain reaction


Quantitative polymerase chain reaction


Inositol phosphate


Phospholipase C


Phospholipase A2


Blood oxygen dependent level


Functional magnetic resonance imaging


Obsessive compulsive disorders


Impulse control disorders


5-Choice serial reaction time task


Extrapyramidal side effects



This work was supported by grants from Centre National de la Recherche Scientifique, Bordeaux University and the European Cooperation in Science and Technology (COST action CM1103). Mélanie Lagière is a fellowship recipient from the Ministère de la Recherche et de l’Enseignement Supérieur. We are grateful to Pr Marie-Françoise Chesselet and Dr Laurence Mignon for discussions about some parts of the manuscript.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • P. De Deurwaerdère
    • 1
    • 2
    Email author
  • M. Lagière
    • 1
    • 2
  • M. Bosc
    • 1
    • 2
  • S. Navailles
    • 1
    • 2
  1. 1.Université de BordeauxBordeaux CedexFrance
  2. 2.Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5293)Université Bordeaux SegalenBordeaux CedexFrance

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