Biological Psychiatry
Volume 67, Issue 12 , Pages 1146-1153 , 15 June 2010

Effects of Early-Life Stress on Serotonin1A Receptors in Juvenile Rhesus Monkeys Measured by Positron Emission Tomography

  • Simona Spinelli

      Affiliations

    • Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Poolesville, Maryland
    • Corresponding Author InformationAddress correspondence to Simona Spinelli, Ph.D., Laboratory for Neurocognitive and Imaging Research, Kennedy Krieger Institute, Johns Hopkins School of Medicine, 716 North Broadway, Baltimore, MD 21205
    • ,
  • Svetlana Chefer

      Affiliations

    • Neuroimaging Research Branch, National Institute on Drug Abuse, Baltimore, Maryland
    • ,
  • Richard E. Carson

      Affiliations

    • PET Center, Department of Radiology, Yale University, New Haven, Connecticut
    • ,
  • Elaine Jagoda

      Affiliations

    • National Institute of Biomedical Imaging and Bioengineering, Bethesda, Maryland
    • ,
  • Lixin Lang

      Affiliations

    • National Institute of Biomedical Imaging and Bioengineering, Bethesda, Maryland
    • ,
  • Markus Heilig

      Affiliations

    • National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
    • ,
  • Christina S. Barr

      Affiliations

    • Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Poolesville, Maryland
    • ,
  • Stephen J. Suomi

      Affiliations

    • Laboratory of Comparative Ethology, National Institute of Child Health and Human Development, Poolesville, Maryland
    • ,
  • J. Dee Higley

      Affiliations

    • Department of Psychology, Brigham Young University, Provo, Utah
    • ,
  • Elliot A. Stein

      Affiliations

    • Neuroimaging Research Branch, National Institute on Drug Abuse, Baltimore, Maryland

Received 31 July 2009 ,Revised 14 December 2009 ,Accepted 26 December 2009.

References 

  1. Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, et al. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology. 2001;25:892–903
  2. Bhagwagar Z, Rabiner EA, Sargent PA, Grasby PM, Cowen PJ. Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635. Mol Psychiatry. 2004;9:386–392
  3. Drevets WC, Thase ME, Moses-Kolko EL, Price J, Frank E, Kupfer DJ, et al. Serotonin-1A receptor imaging in recurrent depression: Replication and literature review. Nucl Med Biol. 2007;34:865–877
  4. Hirvonen J, Karlsson H, Kajander J, Lepola A, Markkula J, Rasi-Hakala H, et al. Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: An in-vivo imaging study using PET and [carbonyl-11C]WAY-100635. Int J Neuropsychopharmacol. 2008;11:465–476
  5. Lanzenberger RR, Mitterhauser M, Spindelegger C, Wadsak W, Klein N, Mien LK, et al. Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry. 2007;61:1081–1089
  6. Nash JR, Sargent PA, Rabiner EA, Hood SD, Argyropoulos SV, Potokar JP, et al. Serotonin 5-HT1A receptor binding in people with panic disorder: Positron emission tomography study. Br J Psychiatry. 2008;193:229–234
  7. Neumeister A, Bain E, Nugent AC, Carson RE, Bonne O, Luckenbaugh DA, et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. 2004;24:589–591
  8. Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, et al. Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: Effects of depression and antidepressant treatment. Arch Gen Psychiatry. 2000;57:174–180
  9. Czesak M, Lemonde S, Peterson EA, Rogaeva A, Albert PR. Cell-specific repressor or enhancer activities of deaf-1 at a serotonin 1A receptor gene polymorphism. J Neurosci. 2006;26:1864–1871
  10. Strobel A, Gutknecht L, Rothe C, Reif A, Mossner R, Zeng Y, et al. Allelic variation in 5-HT1A receptor expression is associated with anxiety- and depression-related personality traits. J Neural Transm. 2003;110:1445–1453
  11. Toth M. 5-HT1A receptor knockout mouse as a genetic model of anxiety. Eur J Pharmacol. 2003;463:177–184
  12. Gross C, Zhuang X, Stark K, Ramboz S, Oosting R, Kirby L, et al. Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature. 2002;416:396–400
  13. Lesch KP, Gutknecht L. Focus on the 5-HT1A receptor: Emerging role of a gene regulatory variant in psychopathology and pharmacogenetics. Int J Neuropsychopharmacol. 2004;7:381–385
  14. Garber J. Depression in children and adolescents: Linking risk research and prevention. Am J Prev Med. 2006;31(suppl 1):S104–S125
  15. Sloan DM, Kornstein SG. Gender differences in depression and response to antidepressant treatment. Psychiatr Clin North Am. 2003;26:581–594
  16. Jovanovic H, Lundberg J, Karlsson P, Cerin A, Saijo T, Varrone A, et al. Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET. Neuroimage. 2008;39:1408–1419
  17. Parsey RV, Oquendo MA, Simpson NR, Ogden RT, Van Heertum R, Arango V, et al. Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor binding potential measured by PET using [C-11]WAY-100635. Brain Res. 2002;954:173–182
  18. Stein P, Savli M, Wadsak W, Mitterhauser M, Fink M, Spindelegger C, et al. The serotonin-1A receptor distribution in healthy men and women measured by PET and [carbonyl-(11)C]WAY-100635. Eur J Nucl Med Mol Imaging. 2008;35:2159–2168
  19. Miller JM, Brennan KG, Ogden TR, Oquendo MA, Sullivan GM, Mann JJ, et al. Elevated serotonin 1A binding in remitted major depressive disorder: Evidence for a trait biological abnormality. Neuropsychopharmacology. 2009;34:2275–2284
  20. Parsey RV, Oquendo MA, Ogden RT, Olvet DM, Simpson N, Huang YY, et al. Altered serotonin 1A binding in major depression: A [carbonyl-C-11]. WAY:100635 positron emission tomography study. Biol Psychiatry. 2006;59:106–113
  21. Teicher MH, Andersen SL, Polcari A, Anderson CM, Navalta CP, Kim DM. The neurobiological consequences of early stress and childhood maltreatment. Neurosci Biobehav Rev. 2003;27:33–44
  22. Jacobs JR, Bovasso GB. Re-examining the long-term effects of experiencing parental death in childhood on adult psychopathology. J Nerv Ment Dis. 2009;197:24–27
  23. Tyrka AR, Wier L, Price LH, Ross N, Anderson GM, Wilkinson CW, et al. Childhood parental loss and adult hypothalamic-pituitary-adrenal function. Biol Psychiatry. 2008;63:1147–1154
  24. Higley JD, Suomi SJ, Linnoila M. A longitudinal assessment of CSF monoamine metabolite and plasma cortisol concentrations in young Rhesus monkeys. Biol Psychiatry. 1992;32:127–145
  25. Ichise M, Vines DC, Gura T, Anderson GM, Suomi SJ, Higley JD, et al. Effects of early life stress on [11C]DASB positron emission tomography imaging of serotonin transporters in adolescent peer- and mother-reared Rhesus monkeys. J Neurosci. 2006;26:4638–4643
  26. Shannon C, Schwandt ML, Champoux M, Shoaf SE, Suomi SJ, Linnoila M, et al. Maternal absence and stability of individual differences in CSF 5-HIAA concentrations in Rhesus monkey infants. Am J Psychiatry. 2005;162:1658–1664
  27. Jagoda EM, Lang L, Tokugawa J, Simmons A, Ma Y, Contoreggi C, et al. Development of 5-HT1A receptor radioligands to determine receptor density and changes in endogenous 5-HT. Synapse. 2006;59:330–341
  28. Carson RE, Lang L, Watabe H, Der MG, Adams HR, Jagoda E, et al. PET evaluation of [(18)F]FCWAY, an analog of the 5-HT(1A) receptor antagonist, WAY-100635. Nucl Med Biol. 2000;27:493–497
  29. Carson RE, Channing MA, Der MG, Herscovitch P, Eckelman WC. Scatchard analysis with bolus/infusion administration of [11C]raclopride; amphetamine effects in anesthetized monkeys. In:  Senda M,  Kimura Y,  Herscovitch P editor. Brain Imaging Using PET. San Diego: Academic; 2002;p. 63–96
  30. Malkova L, Heuer E, Saunders RC. Longitudinal magnetic resonance imaging study of Rhesus monkey brain development. Eur J Neurosci. 2006;24:3204–3212
  31. Lang L, Jagoda E, Schmall B, Sassaman M, Ma Y, Eckelman WC. Fluoroanalogs of WAY-100635 with varying pharmacokinetics properties. Nucl Med Biol. 2000;27:457–462
  32. Ma Y, Lang L, Kiesewetter DO, Jagoda E, Sassaman MB, Der M, et al. Liquid chromatography-tandem mass spectrometry identification of metabolites of two 5-HT1A antagonists, N-[2-[4-(2-methoxylphenyl)piperazino]ethyl]-N-(2-pyridyl) trans- and cis-4-fluorocyclohexanecarboxamide, produced by human and rat hepatocytes. J Chromatogr B Biomed Sci Appl. 2001;755:47–56
  33. Spinelli S, Chefer S, Suomi SJ, Higley JD, Barr CS, Stein EA. Early life stress induces long-term morphological changes in primate brain. Arch Gen Psychiatry. 2009;66:658–665
  34. Liberzon I, Martis B. Neuroimaging studies of emotional responses in PTSD. Ann N Y Acad Sci. 2006;1071:87–109
  35. Stockmeier CA. Involvement of serotonin in depression: Evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psychiatr Res. 2003;37:357–373
  36. Saleem KS, Logothetis NK. A Combined MRI and Histology Atlas of the Rhesus Monkey Brain in Stereotaxic Coordinates. London: Academic Press; 2006;
  37. Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27:1533–1539
  38. Hall H, Lundkvist C, Halldin C, Farde L, Pike VW, McCarron JA, et al. Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain using [3H]WAY-100635 and [11C]WAY-100635. Brain Res. 1997;745:96–108
  39. Akimova E, Lanzenberger R, Kasper S. The Serotonin-1A receptor in anxiety disorders. Biol Psychiatry. 2009;66:627–635
  40. Savitz J, Lucki I, Drevets WC. 5-HT(1A) receptor function in major depressive disorder. Prog Neurobiol. 2009;88:17–31
  41. Shively CA, Friedman DP, Gage HD, Bounds MC, Brown-Proctor C, Blair JB, et al. Behavioral depression and positron emission tomography-determined serotonin 1A receptor binding potential in cynomolgus monkeys. Arch Gen Psychiatry. 2006;63:396–403
  42. Law AJ, Pei Q, Walker MP, Gordon-Andrews H, Weickert CS, Feldon J, et al. Early parental deprivation in the marmoset monkey produces long-term changes in hippocampal expression of genes involved in Synaptic plasticity and implicated in mood disorder. Neuropsychopharmacology. 2008;1–14
  43. Leventopoulos M, Russig H, Feldon J, Pryce CR, Opacka-Juffry J. Early deprivation leads to long-term reductions in motivation for reward and 5-HT1A binding and both effects are reversed by fluoxetine. Neuropharmacology. 2009;56:692–701
  44. Arango V, Underwood MD, Gubbi AV, Mann JJ. Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res. 1995;688:121–133
  45. Szewczyk B, Albert PR, Burns AM, Czesak M, Overholser JC, Jurjus GJ, et al. Gender-specific decrease in NUDR and 5-HT1A receptor proteins in the prefrontal cortex of subjects with major depressive disorder. Int J Neuropsychopharmacol. 2009;12:155–168
  46. Deckersbach T, Dougherty DD, Rauch SL. Functional imaging of mood and anxiety disorders. J Neuroimaging. 2006;16:1–10
  47. Drevets WC, Price JL, Furey ML. Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression. Brain Struct Funct. 2008;213:93–118
  48. Zimmer L, Riad M, Rbah L, Belkacem-Kahlouli A, Le Bars D, Renaud B, et al. Toward brain imaging of serotonin 5-HT1A autoreceptor internalization. Neuroimage. 2004;22:1421–1426
  49. Arborelius L, Eklund MB. Both long and brief maternal separation produces persistent changes in tissue levels of brain monoamines in middle-aged female rats. Neuroscience. 2007;145:738–750
  50. Daniels WM, Pietersen CY, Carstens ME, Daya S, Stein D. Overcrowding induces anxiety and causes loss of serotonin 5HT-1a receptors in rats. Metab Brain Dis. 2000;15:287–295
  51. Simon NM, Zalta AK, Worthington JJ, Hoge EA, Christian KM, Stevens JC, et al. Preliminary support for gender differences in response to fluoxetine for generalized anxiety disorder. Depress Anxiety. 2006;23:373–376
  52. Anand A, Li Y, Wang Y, Gardner K, Lowe MJ. Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: An FMRI study. J Neuropsychiatr Clin Neurosci. 2007;19:274–282
  53. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301:805–809
  54. Borg J. Molecular imaging of the 5-HT(1A) receptor in relation to human cognition. Behav Brain Res. 2008;195:103–111
  55. Cools R, Roberts AC, Robbins TW. Serotoninergic regulation of emotional and behavioural control processes. Trends Cogn Sci. 2008;12:31–40
  56. Evers EA, Cools R, Clark L, van der Veen FM, Jolles J, Sahakian BJ, et al. Serotonergic modulation of prefrontal cortex during negative feedback in probabilistic reversal learning. Neuropsychopharmacology. 2005;30:1138–1147
  57. Taylor Tavares JV, Clark L, Furey ML, Williams GB, Sahakian BJ, Drevets WC. Neural basis of abnormal response to negative feedback in unmedicated mood disorders. Neuroimage. 2008;42:1118–1126
  58. Nelson EE, Herman KN, Barrett CE, Noble PL, Wojteczko K, Chisholm K, et al. Adverse rearing experiences enhance responding to both aversive and rewarding stimuli in juvenile Rhesus monkeys. Biol Psychiatry. 2009;66:702–704
  59. Johns JM, Lubin DA, Lieberman JA, Lauder JM. Developmental effects of prenatal cocaine exposure on 5-HT1A receptors in male and female rat offspring. Dev Neurosci. 2002;24:522–530
  60. Schiller L, Jahkel M, Oehler J. The influence of sex and social isolation housing on pre- and postsynaptic 5-HT1A receptors. Brain Res. 2006;1103:76–87

 Authors SS and SC contributed equally to this work.

PII: S0006-3223(10)00005-3

doi: 10.1016/j.biopsych.2009.12.030

Biological Psychiatry
Volume 67, Issue 12 , Pages 1146-1153 , 15 June 2010

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