Altered 5-HT2C receptor agonist-induced responses and 5-HT2C receptor RNA editing in the amygdala of serotonin transporter knockout mice

BMC Pharmacology

Volumn 11, Issue , 2011, Pages

  Moya, Pablo R ^a   Fox, Meredith A ^a   Jensen, Catherine L ^a   Laporte, Justin L ^a   French, Helen T ^a   Wendland, Jens R ^a   Murphy, Dennis L ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

Author keywords

5 HT2CRNA editingSERTanxiety; amygdala

Indexed keywords

SEROTONIN 2C AGONIST; SEROTONIN 2C RECEPTOR; SEROTONIN TRANSPORTER; (3 CHLOROPHENYL)PIPERAZINE; 1-(3-CHLOROPHENYL)PIPERAZINE; 2 (6 CHLORO 5 FLUORO 1 INDOLYL) 1 METHYLETHYLAMINE; ETHYLAMINE; INDOLE DERIVATIVE; PIPERAZINE DERIVATIVE; RNA PRECURSOR; SEROTONIN 2 AGONIST;

AMYGDALOID NUCLEUS; ANIMAL EXPERIMENT; ANXIETY; ARTICLE; DRUG MECHANISM; MOUSE; NONHUMAN; RNA EDITING; SEROTONIN BLOOD LEVEL; SIGNAL TRANSDUCTION; SNIFFING; SOCIAL INTERACTION; STRESS; ANIMAL; ANIMAL BEHAVIOR; C57BL MOUSE; CHEMICALLY INDUCED DISORDER; DRUG EFFECT; GENETICS; HUMAN RELATION; MALE; METABOLISM; MOUSE MUTANT; PHYSIOLOGY;

AMYGDALA; ANIMALS; ANXIETY; BEHAVIOR, ANIMAL; ETHYLAMINES; INDOLES; INTERPERSONAL RELATIONS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; PIPERAZINES; RECEPTOR, SEROTONIN, 5-HT2C; RNA EDITING; RNA PRECURSORS; SEROTONIN 5-HT2 RECEPTOR AGONISTS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS;

EID: 79953705991     PISSN: None     EISSN: 14712210     Source Type: Journal    
DOI: 10.1186/1471-2210-11-3     Document Type: Article

References (56)

1. Murphy DL, Lesch KP. Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 2008, 9(2):85-96. 10.1038/nrn2284, 18209729.
2. Millan MJ. The neurobiology and control of anxious states. Prog Neurobiol 2003, 70(2):83-244. 10.1016/S0301-0082(03)00087-X, 12927745.
3. Fink KB, Gothert M. 5-HT receptor regulation of neurotransmitter release. Pharmacol Rev 2007, 59(4):360-417.
4. Heisler LK, Pronchuk N, Nonogaki K, Zhou L, Raber J, Tung L, Yeo GS, O'Rahilly S, Colmers WF, Elmquist JK, et al. Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation. J Neurosci 2007, 27(26):6956-6964. 10.1523/JNEUROSCI.2584-06.2007, 17596444.
5. Werry TD, Loiacono R, Sexton PM, Christopoulos A. RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function. Pharmacol Ther 2008, 119(1):7-23. 10.1016/j.pharmthera.2008.03.012, 18554725.
6. Berg KA, Maayani S, Goldfarb J, Scaramellini C, Leff P, Clarke WP. Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus. Mol Pharmacol 1998, 54(1):94-104.
7. McGrew L, Chang MS, Sanders-Bush E. Phospholipase D activation by endogenous 5-hydroxytryptamine 2C receptors is mediated by Galpha13 and pertussis toxin-insensitive Gbetagamma subunits. Mol Pharmacol 2002, 62(6):1339-1343. 10.1124/mol.62.6.1339, 12435801.
8. Werry TD, Gregory KJ, Sexton PM, Christopoulos A. Characterization of serotonin 5-HT2C receptor signaling to extracellular signal-regulated kinases 1 and 2. J Neurochem 2005, 93(6):1603-1615. 10.1111/j.1471-4159.2005.03161.x, 15935077.
9. Fox MA, Jensen CL, French HT, Stein AR, Huang SJ, Tolliver TJ, Murphy DL. Neurochemical, behavioral, and physiological effects of pharmacologically enhanced serotonin levels in serotonin transporter (SERT)-deficient mice. Psychopharmacology (Berl) 2008, 201(2):203-218. 10.1007/s00213-008-1268-7, 2584159, 18712364.
10. Heisler LK, Chu HM, Tecott LH. Epilepsy and obesity in serotonin 5-HT2C receptor mutant mice. Ann N Y Acad Sci 1998, 861:74-78. 10.1111/j.1749-6632.1998.tb10175.x, 9928241.
11. Nonogaki K, Strack AM, Dallman MF, Tecott LH. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med 1998, 4(10):1152-1156. 10.1038/2647, 9771748.
12. Miller KJ. Serotonin 5-ht2c receptor agonists: potential for the treatment of obesity. Mol Interv 2005, 5(5):282-291. 10.1124/mi.5.5.8, 16249524.
13. Qu Y, Villacreses N, Murphy DL, Rapoport SI. 5-HT2A/2C receptor signaling via phospholipase A2 and arachidonic acid is attenuated in mice lacking the serotonin reuptake transporter. Psychopharmacology (Berl) 2005, 180(1):12-20. 10.1007/s00213-005-2231-5, 15834538.
14. Basselin M, Fox MA, Chang L, Bell JM, Greenstein D, Chen M, Murphy DL, Rapoport SI. Imaging elevated brain arachidonic acid signaling in unanesthetized serotonin transporter (5-HTT)-deficient mice. Neuropsychopharmacology 2009, 34(7):1695-1709. 10.1038/npp.2008.227, 2700347, 19145225.
15. Li Q, Wichems CH, Ma L, Van de Kar LD, Garcia F, Murphy DL. Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice. J Neurochem 2003, 84(6):1256-1265. 10.1046/j.1471-4159.2003.01607.x, 12614326.
16. Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 1997, 387(6630):303-308. 10.1038/387303a0, 9153397.
17. Niswender CM, Copeland SC, Herrick-Davis K, Emeson RB, Sanders-Bush E. RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J Biol Chem 1999, 274(14):9472-9478. 10.1074/jbc.274.14.9472, 10092629.
18. Wang Q, O'Brien PJ, Chen CX, Cho DS, Murray JM, Nishikura K. Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors. J Neurochem 2000, 74(3):1290-1300. 10.1046/j.1471-4159.2000.741290.x, 10693963.
19. Price RD, Sanders-Bush E. RNA editing of the human serotonin 5-HT(2C) receptor delays agonist-stimulated calcium release. Mol Pharmacol 2000, 58(4):859-862.
20. Berg KA, Clarke WP, Cunningham KA, Spampinato U. Fine-tuning serotonin2c receptor function in the brain: molecular and functional implications. Neuropharmacology 2008, 55(6):969-976. 10.1016/j.neuropharm.2008.06.014, 18602407.
21. Gurevich I, Tamir H, Arango V, Dwork AJ, Mann JJ, Schmauss C. Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Neuron 2002, 34(3):349-356. 10.1016/S0896-6273(02)00660-8, 11988167.
22. Englander MT, Dulawa SC, Bhansali P, Schmauss C. How stress and fluoxetine modulate serotonin 2C receptor pre-mRNA editing. J Neurosci 2005, 25(3):648-651. 10.1523/JNEUROSCI.3895-04.2005, 15659601.
23. Dracheva S, Chin B, Haroutunian V. Altered serotonin 2C receptor RNA splicing in suicide: association with editing. Neuroreport 2008, 19(3):379-382. 10.1097/WNR.0b013e3282f556d2, 18303585.
24. Gardiner K, Du Y. A-to-I editing of the 5HT2C receptor and behaviour. Brief Funct Genomic Proteomic 2006, 5(1):37-42. 10.1093/bfgp/ell006, 16769676.
25. Bhansali P, Dunning J, Singer SE, David L, Schmauss C. Early life stress alters adult serotonin 2C receptor pre-mRNA editing and expression of the alpha subunit of the heterotrimeric G-protein G q. J Neurosci 2007, 27(6):1467-1473. 10.1523/JNEUROSCI.4632-06.2007, 17287521.
26. Oler JA, Fox AS, Shelton SE, Christian BT, Murali D, Oakes TR, Davidson RJ, Kalin NH. Serotonin transporter availability in the amygdala and bed nucleus of the stria terminalis predicts anxious temperament and brain glucose metabolic activity. J Neurosci 2009, 29(32):9961-9966. 10.1523/JNEUROSCI.0795-09.2009, 2756094, 19675230.
27. Hariri AR, Drabant EM, Munoz KE, Kolachana BS, Mattay VS, Egan MF, Weinberger DR. A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 2005, 62(2):146-152. 10.1001/archpsyc.62.2.146, 15699291.
28. Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D, Egan MF, Weinberger DR. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002, 297(5580):400-403. 10.1126/science.1071829, 12130784.
29. Bagdy G, Graf M, Anheuer ZE, Modos EA, Kantor S. Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635. Int J Neuropsychopharmacol 2001, 4(4):399-408. 10.1017/S1461145701002632, 11806866.
30. Campbell BM, Merchant KM. Serotonin 2C receptors within the basolateral amygdala induce acute fear-like responses in an open-field environment. Brain Res 2003, 993(1-2):1-9. 10.1016/S0006-8993(03)03384-5, 14642825.
31. Herrick-Davis K, Grinde E, Niswender CM. Serotonin 5-HT2C receptor RNA editing alters receptor basal activity: implications for serotonergic signal transduction. J Neurochem 1999, 73(4):1711-1717. 10.1046/j.1471-4159.1999.731711.x, 10501219.
32. Hackler EA, Airey DC, Shannon CC, Sodhi MS, Sanders-Bush E. 5-HT(2C) receptor RNA editing in the amygdala of C57BL/6J, DBA/2J, and BALB/cJ mice. Neurosci Res 2006, 55(1):96-104. 10.1016/j.neures.2006.02.005, 16580757.
33. Du Y, Davisson MT, Kafadar K, Gardiner K. A-to-I pre-mRNA editing of the serotonin 2C receptor: comparisons among inbred mouse strains. Gene 2006, 382:39-46. 10.1016/j.gene.2006.06.007, 16904273.
34. Mathews TA, Fedele DE, Coppelli FM, Avila AM, Murphy DL, Andrews AM. Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expression. J Neurosci Methods 2004, 140(1-2):169-181. 10.1016/j.jneumeth.2004.05.017, 15589347.
35. Gurevich I, Englander MT, Adlersberg M, Siegal NB, Schmauss C. Modulation of serotonin 2C receptor editing by sustained changes in serotonergic neurotransmission. J Neurosci 2002, 22(24):10529-10532.
36. Flomen R, Knight J, Sham P, Kerwin R, Makoff A. Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene. Nucleic Acids Res 2004, 32(7):2113-2122. 10.1093/nar/gkh536, 407821, 15087490.
37. Marion S, Weiner DM, Caron MG. RNA editing induces variation in desensitization and trafficking of 5-hydroxytryptamine 2c receptor isoforms. J Biol Chem 2004, 279(4):2945-2954. 10.1074/jbc.M308742200, 14602721.
38. Porter RH, Malcolm CS, Allen NH, Lamb H, Revell DF, Sheardown MJ. Agonist-induced functional desensitization of recombinant human 5-HT2 receptors expressed in CHO-K1 cells. Biochem Pharmacol 2001, 62(4):431-438. 10.1016/S0006-2952(01)00677-3, 11448452.
39. Silverstone PH, Rue JE, Franklin M, Hallis K, Camplin G, Laver D, Cowen PJ. The effects of administration of mCPP on psychological, cognitive, cardiovascular, hormonal and MHPG measurements in human volunteers. Int Clin Psychopharmacol 1994, 9(3):173-178. 10.1097/00004850-199409000-00005, 7814826.
40. Murphy DL, Mueller EA, Hill JL, Tolliver TJ, Jacobsen FM. Comparative anxiogenic, neuroendocrine, and other physiologic effects of m-chlorophenylpiperazine given intravenously or orally to healthy volunteers. Psychopharmacology (Berl) 1989, 98(2):275-282. 10.1007/BF00444705, 2502799.
41. Kennett GA, Wood MD, Bright F, Trail B, Riley G, Holland V, Avenell KY, Stean T, Upton N, Bromidge S, et al. SB 242084, a selective and brain penetrant 5-HT2C receptor antagonist. Neuropharmacology 1997, 36(4-5):609-620. 10.1016/S0028-3908(97)00038-5, 9225286.
42. Martin JR, Ballard TM, Higgins GA. Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxiety. Pharmacol Biochem Behav 2002, 71(4):615-625. 10.1016/S0091-3057(01)00713-4, 11888553.
43. Nic Dhonnchadha BA, Bourin M, Hascoet M. Anxiolytic-like effects of 5-HT2 ligands on three mouse models of anxiety. Behav Brain Res 2003, 140(1-2):203-214. 10.1016/S0166-4328(02)00311-X, 12644293.
44. Jenck F, Moreau JL, Berendsen HH, Boes M, Broekkamp CL, Martin JR, Wichmann J, Van Delft AM. Antiaversive effects of 5HT2C receptor agonists and fluoxetine in a model of panic-like anxiety in rats. Eur Neuropsychopharmacol 1998, 8(3):161-168. 10.1016/S0924-977X(97)00055-2, 9716307.
45. Salchner P, Singewald N. 5-HT receptor subtypes involved in the anxiogenic-like action and associated Fos response of acute fluoxetine treatment in rats. Psychopharmacology (Berl) 2006, 185(3):282-288. 10.1007/s00213-005-0247-5, 16521035.
46. Dutton AC, Barnes NM. Anti-obesity pharmacotherapy: Future perspectives utilising 5-HT2C receptor agonists. Drug Discovery Today: Therapeutic Strategies 2006, 3(4):577-583.
47. Kim DK, Tolliver TJ, Huang SJ, Martin BJ, Andrews AM, Wichems C, Holmes A, Lesch KP, Murphy DL. Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter. Neuropharmacology 2005, 49(6):798-810. 10.1016/j.neuropharm.2005.08.010, 16183083.
48. Ren-Patterson RF, Cochran LW, Holmes A, Lesch KP, Lu B, Murphy DL. Gender-dependent modulation of brain monoamines and anxiety-like behaviors in mice with genetic serotonin transporter and BDNF deficiencies. Cell Mol Neurobiol 2006, 26(4-6):755-780. 10.1007/s10571-006-9048-6, 17029036.
49. Wendland JR, Moya PR, Kruse MR, Ren-Patterson RF, Jensen CL, Timpano KR, Murphy DL. A novel, putative gain-of-function haplotype at SLC6A4 associates with obsessive-compulsive disorder. Hum Mol Genet 2008, 17(5):717-723. 10.1093/hmg/ddm343, 18055562.
50. Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, et al. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 2006, 78(5):815-826. 10.1086/503850, 1474042, 16642437.
51. Murphy DL, Lerner A, Rudnick G, Lesch KP. Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv 2004, 4(2):109-123. 10.1124/mi.4.2.8, 15087484.
52. Bengel D, Murphy DL, Andrews AM, Wichems CH, Feltner D, Heils A, Mossner R, Westphal H, Lesch KP. Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine ("Ecstasy") in serotonin transporter-deficient mice. Mol Pharmacol 1998, 53(4):649-655.
53. Kuznetsova EG, Amstislavskaya TG, Shefer EA, Popova NK. Effect of 5-HT2C receptor antagonist RS 102221 on mouse behavior. Bull Exp Biol Med 2006, 142(1):76-79. 10.1007/s10517-006-0296-8, 17369908.
54. Gonzalez LE, Andrews N, File SE. 5-HT1A and benzodiazepine receptors in the basolateral amygdala modulate anxiety in the social interaction test, but not in the elevated plus-maze. Brain Res 1996, 732(1-2):145-153. 10.1016/0006-8993(96)00517-3, 8891278.
55. Overstreet DH, Knapp DJ, Moy SS, Breese GR. A 5-HT1A agonist and a 5-HT2c antagonist reduce social interaction deficit induced by multiple ethanol withdrawals in rats. Psychopharmacology (Berl) 2003, 167(4):344-352. 2865243, 12677355.
56. Nadler JJ, Moy SS, Dold G, Trang D, Simmons N, Perez A, Young NB, Barbaro RP, Piven J, Magnuson TR, et al. Automated apparatus for quantitation of social approach behaviors in mice. Genes Brain Behav 2004, 3(5):303-314. 10.1111/j.1601-183X.2004.00071.x, 15344923.