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Cited by 26Neuroendocrine regulation and behaviorAutism Spectrum Disorder ResearchNeurotransmitter Receptor Influence on Behavior

Developmental exposure to a serotonin agonist produces subsequent behavioral and neurochemical changes in the adult male prairie vole

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Martin, Melissa M., Liu, Yan, Wang, Zuoxin·2012·Physiology & Behavior
DOI 10.1016/j.physbeh.2011.09.015PMC PMC3225497
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Abstract

Autistic spectrum disorders (ASDs) are classified as pervasive developmental disorders characterized by abnormalities in various cognitive and behavioral functions. Although exact underlying causes are still unknown, nearly 30% of autistic patients show elevated blood levels of serotonin (5-HT) and, therefore, various genetic and environmental factors that are known to elevate 5-HT levels may play a role in the development of ASDs. In the present study, we used the socially monogamous male prairie vole (Microtus ochrogaster) as an animal model to examine the effects of perinatal exposure to 5-methoxytryptamine (5-MT), a non-selective serotonin agonist, on subsequent behavioral and neurochemical changes in the brain. 5-MT treated males showed a decrease in affiliation and an increase in anxiety-related behavior, as well as a decrease in the density of 5-HT immunoreactive (ir) fibers in the amygdala and oxytocin-ir and vasopressin-ir cells in the paraventricular nucleus of the hypothalamus, compared to saline treated controls. These data indicate that exposure to 5-HT during early development can induce abnormalities in various neurochemical systems which, in turn, may underlie deficits in social and anxiety-related behaviors. In addition, these data will help to establish the prairie vole model to study the neurobiological underpinnings of complex neuropsychiatric disorders such as ASDs.

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  • Manipulation of OT/AVP levels via direct exposures to exogenous hormones, agonists, or alteration of the social environment can significantly modify the number of OT, AVP, and TH neurons in the PVN, resulting in anxiety-like behavior and alterations of prototypical male and female sociosexual behavior.

    “Manipulation of OT/AVP levels via direct exposures to exogenous hormones, agonists, or alteration of the social environment can significantly modify the number of OT, AVP, and TH neurons in the PVN, thereby resulting in anxiety-like behavior and alterations of prototypical male and female sociosexual behavior (123–127).”

    From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [124]

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  1. [2]Ansorge MS Zhou M Lira A Hen R Gingrich JA Early-life blockade of the 5-ht transporter alters emotional behavior in adult mice Science 2004 306 879 81 15514160
  2. [3]Brune CW Kim S-J Salt J Leventhal BL Lord C Cook EH Jr 5-httlpr genotype-specific phenotype in children and adolescents with autism Am J Psychiatry 2006 163 2148 56 17151167
  3. [4]Whitaker-Azmitia PM Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism? Intern J Dev Neurosci 2005 23 75 83 15730889
  4. [5]Cook EH Leventhal BL The serotonin system in autism Curr Opin Pediatr 1996 8 348 54 9053096
  5. [6]Whitaker-Azmitia PM Serotonin and brain development: role in human developmental diseases Brain Res Bull 2001 56 479 85 11750793
  6. [7]Shemer AV Azmitia EC Whitaker-Azmitia PM Dose-related effects of prenatal 5-methoxytryptamine (5-MT) on development of serotonin terminal density and behavior Dev Brain Res 1991 59 59 63 2040080
  7. [8]Lauder JM Krebs H Effects of p-chlorophenylalanine on time of neuronal origin during embryo-genesis in the rat Brain Res 1976 107 638 44 131603
  8. [9]Boylan CB Blue ME Hohmann CF Modeling early cortical serotonergic deficits in autism Behav Brain Res 2007 176 94 108 17034875 PMC2570481
  9. [10]Hohmann CF Walker EM Boylan CB Blue ME Neonatal serotonin depletion alters behavioral responses to spatial change and novelty Brain Res 2007 1139 163 77 17296168 PMC1974858
  10. [11]McNamara IM Borella AW Bialowas LA Whitaker-Azmitia PM Further studies in the developmental hyperserotonemia model (DHS) of autism: social, behavioral and peptide changes Brain Res 2008 1189 203 14 18062943
  11. [12]Young KA Gobrogge KL Liu Y Wang Z The neurobiology of pair bonding: Insights from a socially monogamous rodent Front Neuroendocrin 2011 32 53 69 PMC3012750 20688099
  12. [14]Williams J Catania K Carter C Development of partner preferences in female prairie voles (Microtus ochrogaster): the role of social and sexual experience Horm Behav 1992 26 339 49 1398553
  13. [16]Williams JR Insel TR Harbaugh CR Carter CS Oxytocin administered centrally facilitates formation of a partner preference in female prairie voles (Microtus ochrogaster) J Neuroendocrin 1994 6 247 50 7920590
  14. [20]Villalba C Boyle PA Caliguri EJ De Vries GJ Effects of the selective serotonin reuptake inhibitor fluoxetine on social behaviors in male and female prairie voles (Microtus ochrogaster) Horm Behav 1997 32 184 91 9454669
  15. [22]Roberts RL Wolf KN Sprangel ME Rall WF Wildt DE Prolonged mating in prairie voles (Microtus ochrogaster) increases likelihood of ovulation and embryo number Biol Reprod 1999 60 756 62 10026127
  16. [23]Lauder JM Ontogeny of the serotonergic system in the rat: serotonin as a developmental signal Ann NY Acad Sci 1990 600 297 313 2252317
  17. [24]Whitaker PM Seeman P High-affinity 3H-serotonin binding to caudate: Inhibition by hallucinogens and serotoninergic drugs Psychopharmacology 1978 59 1-5-5 100806
  18. [25]Aghajanian GK Bloom FE The formation of synaptic junctions in developing rat brain: A quantitative electron microscopic study Brain Res 1967 6 716 27 4169903
  19. [26]Shemer A Whitaker-Azmitia PM Azmitia EC Effects of prenatal 5-methoxytryptamine and parachlorophenylalanine on serotonergic uptake and behavior in the neonatal rat Pharm Biochem Behav 1988 30 847 51 2976167
  20. [29]Pan Y Liu Y Young KA Zhang Z Wang Z Post-weaning social isolation alters anxiety-related behavior and neurochemical gene expression in the brain of male prairie voles Neurosci Lett 2009 454 67 71 19429056 PMC2683268
  21. [30]Witt DM Winslow JT Insel TR Enhanced social interactions in rats following chronic, centrally infused oxytocin Pharmacol Biochem Behav 1992 43 855 61 1448480
  22. [31]Insel TR Preston S Winslow JT Mating in the monogamous male: behavioral consequences Physiol Behav 1995 57 615 27 7777594
  23. [32]Stowe JR Liu Y Curtis JT Freeman ME Wang Z Species differences in anxiety-related responses in male prairie and meadow voles: the effects of social isolation Physiol Behav 2005 86 369 78 16115657
  24. [33]Gobrogge KL Liu Y Jia X Wang Z Anterior hypothalamic neural activation and neurochemical associations with aggression in pair-bonded male prairie voles J Comp Neurol 2007 502 1109 22 17444499
  25. [34]Wang ZX Zhou L Hulihan TJ Insel TR Immunoreactivity of central vasopressin and oxytocin pathways in microtine rodents: a quantitative comparative study J Comp Neurol 1996 366 726 37 8833119
  26. [35]Ferguson JN Aldag JM Insel TR Young LJ Oxytocin in the medial amygdala is essential for social recognition in the mouse J Neurosci 2001 21 8278 85 11588199 PMC6763861
  27. [36]Davis M The role of the amygdala in fear and anxiety Palo Alto, CA ETATS-UNIS: Ann Rev 1992 1575447
  28. [37]Neumann Wigger Torner Holsboer Landgraf Brain oxytocin inhibits basal and stress-induced activity of the hypothalamo-pituitary-adrenal axis in male and female rats: partial action within the paraventricular nucleus J Neuroendocrin 2000 12 235 43 10718919
  29. [38]Petrov T Krukoff TL Jhamandas JH Chemically defined collateral projections from the pons to the central nucleus of the amygdala and hypothalamic paraventricular nucleus in the rat Cell Tissue Res 1994 277 289 95 7521791
  30. [39]Kahne D Tudorica A Borella A Shapiro L Johnstone F Huang W Behavioral and magnetic resonance spectroscopic studies in the rat hyperserotonemic model of autism Physiol Behav 2002 75 403 10 11897268
  31. [40]Jamain S Radyushkin K Hammerschmidt K Granon S Boretius S Varoqueaux F Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism Proc Nat Acad Sci, USA 2008 105 1710 15 18227507 PMC2234209
  32. [42]Moy SS Nadler JJ Young NB Perez A Holloway LP Barbaro RP Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains Behav Brain Res 2007 176 4 20 16971002 PMC1857288
  33. [43]Balemans MCM Huibers MMH Eikelenboom NWD Kuipers AJ van Summeren RCJ Pijpers MMCA Reduced exploration, increased anxiety, and altered social behavior: Autistic-like features of euchromatin histone methyltransferase 1 heterozygous knockout mice Behav Brain Res 2010 208 47 55 19896504
  34. [44]Whitaker A Druse PM Walker MP Serotonin as a developmental signal Shannon IRLANDE: Elsevier 1995
  35. [45]Whitaker-Azmitia PM Shemer AV Caruso J Molino L Azmitia EC Role of high affinity serotonin receptors in neuronal growth Ann NY Acad Sci 1990 600 315 30 2252318
  36. [46]Whitaker-Azmitia PM Azmitia EC Autoregulation of fetal serotonergic neuronal development: Role of high affinity serotonin receptors Neurosci Lett 1986 67 307 12 3461314
  37. [48]Hitchcock JM Davis M Fear-potentiated startle using an auditory conditioned stimulus: Effect of lesions of the amygdala Physiol Behav 1987 39 403 08 3575483
  38. [49]Wang RY Aghajanian GK Inhibition of neurons in the amygdala by dorsal raphe stimulation: mediation through a direct serotonergic pathway Brain Res 1977 120 85 102 137766
  39. [50]Stutzmann GE McEwen BS LeDoux JE Serotonin modulation of sensory inputs to the lateral amygdala: dependency on corticosterone J Neurosci 1998 18 9529 38 9801389 PMC6792882
  40. [51]Phelps EA O’Connor KJ Gatenby JC Gore JC Grillon C Davis M Activation of the left amygdala to a cognitive representation of fear Nat Neurosci 2001 4 437 41 11276236
  41. [52]Adolphs R Tranel D Hamann S Young AW Calder AJ Phelps EA Recognition of facial emotion in nine individuals with bilateral amygdala damage Neuropsychologia 1999 37 1111 17 10509833
  42. [54]Carter CS Williams JR Witt DM Insel TR Oxytocin and social bonding Ann NY Acad Sci 1992 652 204 11 1626829
  43. [55]Windle RJ Shanks N Lightman SL Ingram CD Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats Endocrinolgy 1997 138 2829 34 9202224
  44. [58]Kramer KM Cushing BS Carter CS Developmental effects of oxytocin on stress response: single versus repeated exposure Physiol Behav 2003 79 775 82 12954422
  45. [59]Grippo AJ Trahanas DM Zimmerman Ii RR Porges SW Carter CS Oxytocin protects against negative behavioral and autonomic consequences of long-term social isolation Psychoneuroendocrinology 2009 34 1542 53 19553027 PMC2841348
  46. [60]Modahl C Green LA Fein D Morris M Waterhouse L Feinstein C Plasma oxytocin levels in autistic children Biol Psychiatry 1998 43 270 77 9513736
  47. [61]Green LA Fein D Modahl C Feinstein C Waterhouse L Morris M Oxytocin and autistic disorder: alteration in peptide forms Biol Psychiatry 2001 50 609 13 11690596
  48. [62]Hollander E Novotny S Hanratty M Yaffe R DeCaria CM Aronowitz BR Oxytocin infusion reduces repetitive behaviors in adults with autistic and asperger’s disorders Neuropsychopharmacology 2002 28 193 98 12496956
  49. [64]Wotjak CT Kubota M Liebsch G Montkowski A Holsboer F Neumann I Release of vasopressin within the rat paraventricular nucleus in response to emotional stress: a novel mechanism of regulating adrenocorticotropic hormone secretion? J Neurosci 1996 16 7725 32 8922428 PMC6579083
  50. [65]Pitkow LJ Facilitation of affiliation and pair-bond formation by vasopressin receptor gene transfer into the ventral forebrain of a monogamous vole J Neurosci 2001 21 7392 96 11549749 PMC6762997
  51. [66]Kim SJ Young LJ Gonen D Veenstra-VanderWeele J Courchesne R Lord C Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism Mol Psychiatry 2002 7 503 12082568
  52. [68]Yirmiya N Rosenberg C Levi S Salomon S Shulman C Nemanov L Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills Mol Psychiatry 2006 11 488 94 16520824
  53. [70]Hammock EAD Young LJ Oxytocin, vasopressin and pair bonding: implications for autism Philosophical Transactions of the Royal Society B: Biological Sciences 2006 361 2187 98 PMC1764849 17118932

Cited by

Sorted by citations

Authors
Martin, M. M., Liu, Y., & Wang, Z.
Affiliations
Florida State University (US)
Corresponding author
Wang, Zuoxin
ORCID
Venue
Physiology & Behavior
Publisher
Elsevier BV
Published
2012-01
Volume
105
Issue
2
Pages
529-535
ISSN
0031-9384 (ISSN-L)
DOI
10.1016/j.physbeh.2011.09.015
PMC
PMC3225497
OpenAlex
W2228034835
Cited by
26
References
22
Citations by year
2022: 1 · 2021: 2 · 2020: 6 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 2
FWCI
3.49
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Physiology & Behavior (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
serotonin receptor agonists, 5-methoxytryptamine, perinatal exposure, autism spectrum disorder, Microtus ochrogaster, social affiliation, anxiety-like behavior, serotonin immunoreactivity, amygdala, oxytocin, vasopressin, paraventricular nucleus, social monogamy, animal models of autism
MeSH terms
Animals, Arginine Vasopressin, Behavior, Animal, Brain, Arvicolinae, Exploratory Behavior, Female, Male, 5-Methoxytryptamine, Neurochemistry, Pregnancy, Prenatal Exposure Delayed Effects, Serotonin, Social Behavior, Serotonin Receptor Agonists, Maze Learning

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