Fine-tuning serotonin2c receptor function in the brain: Molecular and functional implications

The serotonin(2C) receptor (5-HT(2C)R) is a member of the serotonin(2) family of 7-transmembrane-spanning (7-TMS) receptors, which possesses unique molecular and pharmacological properties such as constitutive activity and RNA editing. The 5-HT(2C)R is widely expressed within the central nervous system, where is thought to play a major role in the regulation of neuronal network excitability. In keeping with its ability to modulate dopamine (DA) neuron function in the brain, the 5-HT(2C)R is currently considered as a major target for improved treatments of neuropsychiatric disorders related to DA neuron dysfunction, such as depression, schizophrenia, Parkinson's disease or drug addiction. The aim of this review is to provide an update of the functional status of the central 5-HT(2C)R, covering molecular, cellular, anatomical, biochemical and behavioral aspects to highlight its distinctive regulatory properties, the emerging functional significance of constitutive activity and RNA editing in vivo, and the therapeutic potential of inverse agonism.

[1]  S. Henriksen,et al.  Electrophysiological Characterization of GABAergic Neurons in the Ventral Tegmental Area , 1998, The Journal of Neuroscience.

[2]  P. Sexton,et al.  Mechanisms of ERK1/2 regulation by seven-transmembrane-domain receptors. , 2006, Current pharmaceutical design.

[3]  Trevor Sharp,et al.  A review of central 5-HT receptors and their function , 1999, Neuropharmacology.

[4]  D. Nelson,et al.  Receptor subtype and density determine the coupling repertoire of the 5-HT2 receptor subfamily. , 1996, Life sciences.

[5]  J. Dunlop,et al.  A Conservative, Single-Amino Acid Substitution in the Second Cytoplasmic Domain of the Human Serotonin2C Receptor Alters Both Ligand-Dependent and -Independent Receptor Signaling , 2008, Journal of Pharmacology and Experimental Therapeutics.

[6]  B. Largent,et al.  High‐Affinity Agonist Binding Correlates with Efficacy (Intrinsic Activity) at the Human Serotonin 5‐HT2A and 5‐HT2C Receptors: Evidence Favoring the Ternary Complex and Two‐State Models of Agonist Action , 1999, Journal of neurochemistry.

[7]  P. De Deurwaerdère,et al.  Constitutive Activity of the Serotonin2C Receptor Inhibits In Vivo Dopamine Release in the Rat Striatum and Nucleus Accumbens , 2004, The Journal of Neuroscience.

[8]  U. Spampinato,et al.  Selective blockade of serotonin-2C/2B receptors enhances mesolimbic and mesostriatal dopaminergic function: a combined in vivo electrophysiological and microdialysis study , 1999, Neuroscience.

[9]  B. Roth The serotonin receptors : from molecular pharmacology to human therapeutics , 2006 .

[10]  K. Cunningham,et al.  Role of 5-HT2A and 5-HT2B/2C Receptors in the Behavioral Interactions Between Serotonin and Catecholamine Reuptake Inhibitors , 2001, Neuropsychopharmacology.

[11]  L. M. Leeb-Lundberg,et al.  Negative and Positive Regulatory Epitopes in the C-Terminal Domains of the Human B1 and B2 Bradykinin Receptor Subtypes Determine Receptor Coupling Efficacy to G9/11-Mediated Phospholipase Cβ Activity , 2002 .

[12]  W. Sadee,et al.  Hydrophobic amino acid in the i2 loop plays a key role in receptor-G protein coupling. , 1993, The Journal of biological chemistry.

[13]  J. Harvey,et al.  Physiological relevance of constitutive activity of 5-HT2A and 5-HT2C receptors. , 2005, Trends in pharmacological sciences.

[14]  M. Castagna,et al.  Distribution and cellular localization of the serotonin type 2C receptor messenger RNA in human brain , 1999, Neuroscience.

[15]  M. Héry,et al.  Serotonin-Induced Increases in Adult Cell Proliferation and Neurogenesis are Mediated Through Different and Common 5-HT Receptor Subtypes in the Dentate Gyrus and the Subventricular Zone , 2004, Neuropsychopharmacology.

[16]  E. sanders-Bush,et al.  Deletion of the Serotonin 5-HT2C Receptor PDZ Recognition Motif Prevents Receptor Phosphorylation and Delays Resensitization of Receptor Responses* , 2000, The Journal of Biological Chemistry.

[17]  N. Volkow,et al.  The neural basis of addiction: a pathology of motivation and choice. , 2005, The American journal of psychiatry.

[18]  Arthur Christopoulos,et al.  Functional Selectivity and Classical Concepts of Quantitative Pharmacology , 2007, Journal of Pharmacology and Experimental Therapeutics.

[19]  M. Caron,et al.  RNA Editing Induces Variation in Desensitization and Trafficking of 5-Hydroxytryptamine 2c Receptor Isoforms* , 2004, Journal of Biological Chemistry.

[20]  E. Esposito,et al.  Serotonin-dopamine interaction in the rat ventral tegmental area: an electrophysiological study in vivo. , 1994, The Journal of pharmacology and experimental therapeutics.

[21]  P Ghanouni,et al.  Mutation of a highly conserved aspartic acid in the beta2 adrenergic receptor: constitutive activation, structural instability, and conformational rearrangement of transmembrane segment 6. , 1999, Molecular pharmacology.

[22]  E. Esposito,et al.  Selective stimulation of serotonin2C receptors blocks the enhancement of striatal and accumbal dopamine release induced by nicotine administration , 2004, Journal of neurochemistry.

[23]  J. Palacios,et al.  Regional distribution and cellular localization of 5‐HT2C receptor mRNA in monkey brain: Comparison with [3H]mesulergine binding sites and choline acetyltransferase mRNA , 2001, Synapse.

[24]  L. Tecott,et al.  Contributions of 5-HT(2C) receptors to multiple actions of central serotonin systems. , 2004, European journal of pharmacology.

[25]  R. Leurs,et al.  The effect of mutations in the DRY motif on the constitutive activity and structural instability of the histamine H(2) receptor. , 2000, Molecular pharmacology.

[26]  J. Palacios,et al.  The distribution and cellular localization of the serotonin 1C receptor mRNA in the rodent brain examined by in situ hybridization histochemistry. Comparison with receptor binding distribution , 1990, Neuroscience.

[27]  Sudhir C. Sharma,et al.  Design, synthesis, and evaluation of linear and cyclic peptide ligands for PDZ10 of the multi-PDZ domain protein MUPP1. , 2007, Biochemistry.

[28]  Yasuhiro Kaneda,et al.  Serotonin receptors : their key role in drugs to treat schizophrenia , 2003, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[29]  J. Mazurkiewicz,et al.  Inhibition of Serotonin 5-Hydroxytryptamine2C Receptor Function through Heterodimerization , 2005, Journal of Biological Chemistry.

[30]  Y. Sugimoto,et al.  A Cluster of Aromatic Amino Acids in the i2 Loop Plays a Key Role for Gs Coupling in Prostaglandin EP2 and EP3 Receptors* , 2004, Journal of Biological Chemistry.

[31]  Erwan Bezard,et al.  Novel pharmacological targets for the treatment of Parkinson's disease , 2006, Nature Reviews Drug Discovery.

[32]  P. De Deurwaerdère,et al.  Role of Serotonin2A and Serotonin2B/2C Receptor Subtypes in the Control of Accumbal and Striatal Dopamine Release Elicited In Vivo by Dorsal Raphe Nucleus Electrical Stimulation , 1999, Journal of neurochemistry.

[33]  S. Maayani,et al.  Differences in rapid desensitization of 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptor-mediated phospholipase C activation. , 2001, The Journal of pharmacology and experimental therapeutics.

[34]  C. Schmauss Regulation of serotonin 2C receptor pre-mRNA editing by serotonin. , 2005, International review of neurobiology.

[35]  K. Cunningham,et al.  Validation of a selective serotonin 5-HT2C receptor antibody for utilization in fluorescence immunohistochemistry studies , 2005, Brain Research.

[36]  Kathryn A. Cunningham,et al.  Serotonergic mechanisms in addiction-related memories , 2008, Behavioural Brain Research.

[37]  T. Yamaji,et al.  Activation of the serotonin 5-HT2C receptor is involved in the enhanced anxiety in rats after single-prolonged stress , 2008, Pharmacology Biochemistry and Behavior.

[38]  K. Cunningham,et al.  Distribution of serotonin 5-HT2C receptors in the ventral tegmental area , 2007, Neuroscience.

[39]  M. Millan,et al.  Inverse Agonist and Neutral Antagonist Actions of Antidepressants at Recombinant and Native 5-Hydroxytryptamine2C Receptors: Differential Modulation of Cell Surface Expression and Signal Transduction , 2008, Molecular Pharmacology.

[40]  P. De Deurwaerdère,et al.  The nigrostriatal dopamine system: a neglected target for 5-HT2C receptors. , 2001, TIPS - Trends in Pharmacological Sciences.

[41]  A. Scheer,et al.  Mutational analysis of the highly conserved arginine within the Glu/Asp-Arg-Tyr motif of the alpha(1b)-adrenergic receptor: effects on receptor isomerization and activation. , 2000, Molecular pharmacology.

[42]  B. Goñi-Allo,et al.  Administration of SCH 23390 into the Medial Prefrontal Cortex Blocks the Expression of MDMA-Induced Behavioral Sensitization in Rats: An Effect Mediated by 5-HT2C Receptor Stimulation and not by D1 Receptor Blockade , 2005, Neuropsychopharmacology.

[43]  M. Millan,et al.  Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. , 2005, Therapie.

[44]  U. Spampinato,et al.  The effect of serotonergic agents on haloperidol-induced striatal dopamine release in vivo: opposite role of 5-HT2A and 5-HT2C receptor subtypes and significance of the haloperidol dose used , 2000, Neuropharmacology.

[45]  J. Palacios,et al.  Mapping of 5‐HT2A receptors and their mRNA in monkey brain: [3H]MDL100,907 autoradiography and in situ hybridization studies , 2001, The Journal of comparative neurology.

[46]  J. Tam,et al.  Dissecting G Protein-coupled Receptor Signaling Pathways with Membrane-permeable Blocking Peptides , 2000, The Journal of Biological Chemistry.

[47]  E. Esposito,et al.  Selective activation of 5-HT2C receptors stimulates GABA-ergic function in the rat substantia nigra pars reticulata: A combined in vivo electrophysiological and neurochemical study , 2007, Neuroscience.

[48]  J. Leysen,et al.  5-HT2 receptors. , 2004, Current drug targets. CNS and neurological disorders.

[49]  M. Caron,et al.  A β-Arrestin Binding Determinant Common to the Second Intracellular Loops of Rhodopsin Family G Protein-coupled Receptors* , 2006, Journal of Biological Chemistry.

[50]  E. sanders-Bush,et al.  RNA editing of the human serotonin 5-HT2C receptor disrupts transactivation of the small G-protein RhoA. , 2004, Molecular pharmacology.

[51]  P. Leff,et al.  Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus. , 1998, Molecular pharmacology.

[52]  K. Merchant,et al.  Serotonin 2C receptors within the basolateral amygdala induce acute fear-like responses in an open-field environment , 2003, Brain Research.

[53]  L. Pozzi,et al.  Stimulation of 5‐hydroxytryptamine (5‐HT2C) receptors in the ventrotegmental area inhibits stress‐induced but not basal dopamine release in the rat prefrontal cortex , 2002, Journal of neurochemistry.

[54]  U. Spampinato,et al.  5-HT2A and 5-HT2C/2B Receptor Subtypes Modulate Dopamine Release Induced in Vivo by Amphetamine and Morphine in Both the Rat Nucleus Accumbens and Striatum , 2002, Neuropsychopharmacology.

[55]  V. Grutta,et al.  m-Chlorophenylpiperazine excites non-dopaminergic neurons in the rat substantia nigra and ventral tegmental area by activating serotonin-2C receptors , 2001, Neuroscience.

[56]  J. Bockaert,et al.  Constitutively active mutants of 5‐HT4 receptors are they in unique active states? , 2001, EMBO reports.

[57]  E. Esposito,et al.  Serotonin/dopamine interaction--focus on 5-HT2C receptor, a new target of psychotropic drugs. , 2002, Indian journal of experimental biology.

[58]  E. Esposito,et al.  Role of 5-HT(2C) receptors in the control of central dopamine function. , 2001, Trends in pharmacological sciences.

[59]  C. Niswender,et al.  Serotonin 5‐HT2C Receptor RNA Editing Alters Receptor Basal Activity , 1999, Journal of neurochemistry.

[60]  M. Filip,et al.  Hyperlocomotive and Discriminative Stimulus Effects of Cocaine Are Under the Control of Serotonin2C (5-HT2C) Receptors in Rat Prefrontal Cortex , 2003, Journal of Pharmacology and Experimental Therapeutics.

[61]  H. Meltzer,et al.  Serotonin 5-HT2C agonists selectively inhibit morphine-induced dopamine efflux in the nucleus accumbens , 1998, Brain Research.

[62]  Q. Yan Activation of 5-HT2A/2C receptors within the nucleus accumbens increases local dopaminergic transmission , 2000, Brain Research Bulletin.

[63]  H. McFarlane,et al.  Modulation of dopamine release by striatal 5‐HT2C receptors , 2005, Synapse.

[64]  M. Filip,et al.  Serotonin 5-HT2C receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine , 2002, Pharmacology Biochemistry and Behavior.

[65]  J. Mazurkiewicz,et al.  Biochemical and biophysical characterization of serotonin 5-HT2C receptor homodimers on the plasma membrane of living cells. , 2004, Biochemistry.

[66]  D. Overstreet,et al.  Hyperfunctionality of serotonin-2C receptor-mediated inhibition of accumbal dopamine release in an animal model of depression is reversed by antidepressant treatment , 2005, Neuropharmacology.

[67]  S. Sesack,et al.  Dopamine terminals synapse on callosal projection neurons in the rat prefrontal cortex , 2000, The Journal of comparative neurology.

[68]  U. Spampinato,et al.  Clozapine and Haloperidol Differentially Alter the Constitutive Activity of Central Serotonin2C Receptors In Vivo , 2006, Biological Psychiatry.

[69]  J. Arthur,et al.  5-HT Receptor Signal Transduction Pathways , 2006 .

[70]  P. Moya,et al.  Functional Selectivity of Hallucinogenic Phenethylamine and Phenylisopropylamine Derivatives at Human 5-Hydroxytryptamine (5-HT)2A and 5-HT2C Receptors , 2007, Journal of Pharmacology and Experimental Therapeutics.

[71]  M. Millan,et al.  Differential activation of Gq/11 and Gi(3) proteins at 5-hydroxytryptamine(2C) receptors revealed by antibody capture assays: influence of receptor reserve and relationship to agonist-directed trafficking. , 2002, Molecular pharmacology.

[72]  M. Yanagisawa,et al.  A consensus sequence in the endothelin-B receptor second intracellular loop is required for NHE3 activation by endothelin-1. , 2005, American journal of physiology. Renal physiology.

[73]  K. Uryu,et al.  Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats , 1997, The Journal of comparative neurology.

[74]  Philippe Marin,et al.  The Serotonin 5-HT2A and 5-HT2C Receptors Interact with Specific Sets of PDZ Proteins* , 2004, Journal of Biological Chemistry.

[75]  K. Cunningham,et al.  Serotonin2C receptor localization in GABA neurons of the rat medial prefrontal cortex: Implications for understanding the neurobiology of addiction , 2007, Neuroscience.

[76]  D. Dinh,et al.  Positive allosteric modulator of the human 5-HT2C receptor. , 2003, Molecular pharmacology.

[77]  Bryan L Roth,et al.  Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex , 2006, Neuropsychopharmacology.

[78]  E. sanders-Bush,et al.  Agonist-Directed Signaling of Serotonin 5-HT2C Receptors: Differences Between Serotonin and Lysergic Acid Diethylamide (LSD) , 1999, Neuropsychopharmacology.

[79]  S. Hyman,et al.  Neural mechanisms of addiction: the role of reward-related learning and memory. , 2006, Annual review of neuroscience.

[80]  K. Nishikura,et al.  Altered G Protein‐Coupling Functions of RNA Editing Isoform and Splicing Variant Serotonin2C Receptors , 2000, Journal of neurochemistry.

[81]  L. Bristow,et al.  Activation of mesolimbic dopamine function by phencyclidine is enhanced by 5-HT2C/2B receptor antagonists: neurochemical and behavioural studies , 2000, Neuropharmacology.

[82]  P. Whitton,et al.  Anxiogenic-like effect of infusing 1-(3-chlorophenyl) piperazine (mCPP) into the hippocampus , 2005, Psychopharmacology.

[83]  C. Wichems,et al.  Brain region‐specific alterations of 5‐HT2A and 5‐HT2C receptors in serotonin transporter knockout mice , 2003, Journal of neurochemistry.

[84]  Arthur Christopoulos,et al.  RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function. , 2008, Pharmacology & therapeutics.

[85]  A. Lawrence,et al.  Characterisation of agonist binding on human 5-HT2C receptor isoforms. , 2001, European journal of pharmacology.

[86]  P. Fletcher,et al.  Injection of the 5-HT2C Receptor Agonist Ro60-0175 into the Ventral Tegmental Area Reduces Cocaine-Induced Locomotor Activity and Cocaine Self-Administration , 2004, Neuropsychopharmacology.

[87]  K. Berg,et al.  Development of functionally selective agonists as novel therapeutic agents , 2006 .

[88]  E. Pehek,et al.  Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. , 2007, Pharmacology & therapeutics.

[89]  D. Wright,et al.  Comparative localization of serotonin1A, 1C, and 2 receptor subtype mRNAs in rat brain , 1995, The Journal of comparative neurology.

[90]  R. Lefkowitz,et al.  Ligand-induced overexpression of a constitutively active beta2-adrenergic receptor: pharmacological creation of a phenotype in transgenic mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[91]  M. Koch,et al.  Activation of the brain 5-HT2C receptors causes hypolocomotion without anxiogenic-like cardiovascular adjustments in mice , 2007, Neuropharmacology.

[92]  M. Millan,et al.  Serotonin2C receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic, but not serotonergic, pathways: A combined dialysis and electrophysiological analysis in the rat , 2000, Synapse.

[93]  B. Yamamoto,et al.  Serotonin–GABA interactions modulate MDMA‐induced mesolimbic dopamine release , 2004, Journal of neurochemistry.

[94]  K. Gregory,et al.  Characterization of serotonin 5‐HT2C receptor signaling to extracellular signal‐regulated kinases 1 and 2 , 2005, Journal of neurochemistry.

[95]  Colleen M. Niswender,et al.  RNA Editing of the Human Serotonin 5-Hydroxytryptamine 2C Receptor Silences Constitutive Activity* , 1999, The Journal of Biological Chemistry.

[96]  S. Sesack,et al.  Anatomical Substrates for Glutamate‐Dopamine Interactions , 2003 .

[97]  M. Pompeiano,et al.  Localization of the mRNA for the 5-HT2 receptor by in situ hybridization histochemistry. Correlation with the distribution of receptor sites , 1990, Brain Research.

[98]  M. Brann,et al.  The Second Intracellular Loop of the m5 Muscarinic Receptor Is the Switch Which Enables G-protein Coupling* , 1998, The Journal of Biological Chemistry.

[99]  U. Spampinato,et al.  Differential Effects of 5-Methyl-1-[[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl]-6-trifluoromethylindone (SB 243213) on 5-Hydroxytryptamine2C Receptor-Mediated Responses , 2006, Journal of Pharmacology and Experimental Therapeutics.

[100]  U. Spampinato,et al.  In Vivo Evidence that 5-HT2C Receptor Antagonist but not Agonist Modulates Cocaine-Induced Dopamine Outflow in the Rat Nucleus Accumbens and Striatum , 2004, Neuropsychopharmacology.

[101]  K. Cunningham,et al.  Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence. , 2006, Current topics in medicinal chemistry.

[102]  C. Flanagan,et al.  A GPCR That Is Not “DRY” , 2005, Molecular Pharmacology.

[103]  S. Maayani,et al.  Novel actions of inverse agonists on 5-HT2C receptor systems. , 1999, Molecular pharmacology.

[104]  U. Spampinato,et al.  Role of Striatal Serotonin2A and Serotonin2C Receptor Subtypes in the Control of In Vivo Dopamine Outflow in the Rat Striatum , 2000, Journal of neurochemistry.

[105]  R. Malenka,et al.  Synaptic plasticity and addiction , 2007, Nature Reviews Neuroscience.

[106]  Christian A. Heidbreder,et al.  5‐HT2C receptor antagonists: Potential in schizophrenia , 2001 .

[107]  E. Esposito,et al.  Stimulation of Serotonin2C Receptors Blocks the Hyperactivation of Midbrain Dopamine Neurons Induced by Nicotine Administration , 2004, Journal of Pharmacology and Experimental Therapeutics.

[108]  Paul J. Harrison,et al.  The distribution of 5-HT1A and 5-HT2A receptor mRNA in human brain , 1995, Brain Research.

[109]  W. Im,et al.  Agonist-induced GTPγ35S binding mediated by human 5-HT2C receptors expressed in human embryonic kidney 293 cells , 1999 .

[110]  U. Spampinato,et al.  Differential Regulation of the Mesoaccumbens Dopamine Circuit by Serotonin2C Receptors in the Ventral Tegmental Area and the Nucleus Accumbens: An In Vivo Microdialysis Study with Cocaine , 2008, Neuropsychopharmacology.

[111]  Brian K. Kobilka,et al.  Structural Instability of a Constitutively Active G Protein-coupled Receptor , 1997, The Journal of Biological Chemistry.

[112]  U. Spampinato,et al.  Region‐dependent regulation of mesoaccumbens dopamine neurons in vivo by the constitutive activity of central serotonin2C receptors , 2006, Journal of neurochemistry.

[113]  D. Albrecht,et al.  5‐HT1A receptor‐mediated inhibition and 5‐HT2 as well as 5‐HT3 receptor‐mediated excitation in different subdivisions of the rat amygdala , 2000, Synapse.

[114]  M. Teitler,et al.  Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. , 2000, The Journal of pharmacology and experimental therapeutics.

[115]  John C Gore,et al.  5-Hydroxytryptamine2C Receptor Contribution to m-Chlorophenylpiperazine and N-Methyl-β-carboline-3-carboxamide-Induced Anxiety-Like Behavior and Limbic Brain Activation , 2007, Journal of Pharmacology and Experimental Therapeutics.

[116]  E. V. Bockstaele,et al.  GABA-containing neurons in the ventral tegmental area project to the nucleus accumbens in rat brain , 1995, Brain Research.

[117]  R. Emeson,et al.  RNA‐editing of the 5‐HT2C receptor alters agonist‐receptor‐effector coupling specificity , 2001, British journal of pharmacology.

[118]  A. Meneses,et al.  Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in learning , 1997, Behavioural Brain Research.

[119]  M. Pompeiano,et al.  Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. , 1994, Brain research. Molecular brain research.

[120]  T. Blackburn,et al.  Immunohistochemical localisation of the 5-HT2C receptor protein in the rat CNS , 2000, Neuropharmacology.

[121]  Q. Wan,et al.  Disruption of PTEN coupling with 5-HT2C receptors suppresses behavioral responses induced by drugs of abuse , 2006, Nature Medicine.

[122]  O. Phillipson The cytoarchitecture of the interfascicular nucleus and ventral tegmental area of tsai in the rat , 1979, The Journal of comparative neurology.

[123]  E. sanders-Bush,et al.  Phospholipase D activation by endogenous 5-hydroxytryptamine 2C receptors is mediated by Galpha13 and pertussis toxin-insensitive Gbetagamma subunits. , 2002, Molecular pharmacology.

[124]  J. Mazurkiewicz,et al.  Serotonin 5-HT2C Receptor Homodimer Biogenesis in the Endoplasmic Reticulum , 2006, Journal of Biological Chemistry.

[125]  L. Swanson,et al.  The projections of the ventral tegmental area and adjacent regions: A combined fluorescent retrograde tracer and immunofluorescence study in the rat , 1982, Brain Research Bulletin.

[126]  R. Emeson,et al.  Regulation of serotonin-2C receptor G-protein coupling by RNA editing , 1997, Nature.

[127]  D. Weiner,et al.  RNA Editing of the Human Serotonin 5-HT2CReceptor Alters Receptor-mediated Activation of G13Protein* , 2001, The Journal of Biological Chemistry.