Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism

Jill L Silverman, M. Yang, S. M. Turner, A. M. Katz, D. B. Bell, J. I. Koenig, Jacqueline Crawley

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including low social interactions, reduced vocalizations in social settings, and high levels of repetitive self-grooming. Autism-relevant phenotypes in BTBR offer translational tools to discover neurochemical mechanisms underlying unusual mouse behaviors relevant to symptoms of autism. Because repetitive self-grooming in mice may be a displacement behavior elevated by stressors, we investigated neuroendocrine markers of stress and behavioral reactivity to stressors in BTBR mice, as compared to C57BL/6J (B6), a standard inbred strain with high sociability. Radioimmunoassays replicated previous findings that circulating corticosterone is higher in BTBR than in B6. Higher basal glucocorticoid receptor mRNA and higher oxytocin peptide levels were detected in the brains of BTBR as compared to B6. No significant differences were detected in corticotrophin releasing factor (CRF) peptide or CRF mRNA. In response to behavioral stressors, BTBR and B6 were generally similar on behavioral tasks including stress-induced hyperthermia, elevated plus-maze, light ↔ dark exploration, tail flick, acoustic startle and prepulse inhibition. BTBR displayed less reactivity than B6 to a noxious thermal stimulus in the hot plate, and less immobility than B6 in both the forced swim and tail suspension depression-related tasks. BTBR, therefore, exhibited lower depression-like scores than B6 on two standard tests sensitive to antidepressants, did not differ from B6 on two well-validated anxiety-like behaviors, and did not exhibit unusual stress reactivity to sensory stimuli. Our findings support the interpretation that autism-relevant social deficits, vocalizations, and repetitive behaviors are not the result of abnormal stress reactivity in the BTBR mouse model of autism.

Original languageEnglish (US)
Pages (from-to)1197-1208
Number of pages12
JournalNeuroscience
Volume171
Issue number4
DOIs
StatePublished - Dec 29 2010
Externally publishedYes

Fingerprint

Autistic Disorder
Grooming
Corticotropin-Releasing Hormone
Interpersonal Relations
Depression
Hindlimb Suspension
Phenotype
Messenger RNA
Peptides
Induced Hyperthermia
Inbred Strains Mice
Glucocorticoid Receptors
Oxytocin
Corticosterone
Acoustics
Antidepressive Agents
Radioimmunoassay
Tail
Anxiety
Hot Temperature

Keywords

  • Autism
  • BTBR
  • Mouse models

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism. / Silverman, Jill L; Yang, M.; Turner, S. M.; Katz, A. M.; Bell, D. B.; Koenig, J. I.; Crawley, Jacqueline.

In: Neuroscience, Vol. 171, No. 4, 29.12.2010, p. 1197-1208.

Research output: Contribution to journalArticle

Silverman, Jill L ; Yang, M. ; Turner, S. M. ; Katz, A. M. ; Bell, D. B. ; Koenig, J. I. ; Crawley, Jacqueline. / Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism. In: Neuroscience. 2010 ; Vol. 171, No. 4. pp. 1197-1208.
@article{e701f1d79b0c4b5b9be1d88209bf593b,
title = "Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism",
abstract = "Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including low social interactions, reduced vocalizations in social settings, and high levels of repetitive self-grooming. Autism-relevant phenotypes in BTBR offer translational tools to discover neurochemical mechanisms underlying unusual mouse behaviors relevant to symptoms of autism. Because repetitive self-grooming in mice may be a displacement behavior elevated by stressors, we investigated neuroendocrine markers of stress and behavioral reactivity to stressors in BTBR mice, as compared to C57BL/6J (B6), a standard inbred strain with high sociability. Radioimmunoassays replicated previous findings that circulating corticosterone is higher in BTBR than in B6. Higher basal glucocorticoid receptor mRNA and higher oxytocin peptide levels were detected in the brains of BTBR as compared to B6. No significant differences were detected in corticotrophin releasing factor (CRF) peptide or CRF mRNA. In response to behavioral stressors, BTBR and B6 were generally similar on behavioral tasks including stress-induced hyperthermia, elevated plus-maze, light ↔ dark exploration, tail flick, acoustic startle and prepulse inhibition. BTBR displayed less reactivity than B6 to a noxious thermal stimulus in the hot plate, and less immobility than B6 in both the forced swim and tail suspension depression-related tasks. BTBR, therefore, exhibited lower depression-like scores than B6 on two standard tests sensitive to antidepressants, did not differ from B6 on two well-validated anxiety-like behaviors, and did not exhibit unusual stress reactivity to sensory stimuli. Our findings support the interpretation that autism-relevant social deficits, vocalizations, and repetitive behaviors are not the result of abnormal stress reactivity in the BTBR mouse model of autism.",
keywords = "Autism, BTBR, Mouse models",
author = "Silverman, {Jill L} and M. Yang and Turner, {S. M.} and Katz, {A. M.} and Bell, {D. B.} and Koenig, {J. I.} and Jacqueline Crawley",
year = "2010",
month = "12",
day = "29",
doi = "10.1016/j.neuroscience.2010.09.059",
language = "English (US)",
volume = "171",
pages = "1197--1208",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism

AU - Silverman, Jill L

AU - Yang, M.

AU - Turner, S. M.

AU - Katz, A. M.

AU - Bell, D. B.

AU - Koenig, J. I.

AU - Crawley, Jacqueline

PY - 2010/12/29

Y1 - 2010/12/29

N2 - Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including low social interactions, reduced vocalizations in social settings, and high levels of repetitive self-grooming. Autism-relevant phenotypes in BTBR offer translational tools to discover neurochemical mechanisms underlying unusual mouse behaviors relevant to symptoms of autism. Because repetitive self-grooming in mice may be a displacement behavior elevated by stressors, we investigated neuroendocrine markers of stress and behavioral reactivity to stressors in BTBR mice, as compared to C57BL/6J (B6), a standard inbred strain with high sociability. Radioimmunoassays replicated previous findings that circulating corticosterone is higher in BTBR than in B6. Higher basal glucocorticoid receptor mRNA and higher oxytocin peptide levels were detected in the brains of BTBR as compared to B6. No significant differences were detected in corticotrophin releasing factor (CRF) peptide or CRF mRNA. In response to behavioral stressors, BTBR and B6 were generally similar on behavioral tasks including stress-induced hyperthermia, elevated plus-maze, light ↔ dark exploration, tail flick, acoustic startle and prepulse inhibition. BTBR displayed less reactivity than B6 to a noxious thermal stimulus in the hot plate, and less immobility than B6 in both the forced swim and tail suspension depression-related tasks. BTBR, therefore, exhibited lower depression-like scores than B6 on two standard tests sensitive to antidepressants, did not differ from B6 on two well-validated anxiety-like behaviors, and did not exhibit unusual stress reactivity to sensory stimuli. Our findings support the interpretation that autism-relevant social deficits, vocalizations, and repetitive behaviors are not the result of abnormal stress reactivity in the BTBR mouse model of autism.

AB - Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including low social interactions, reduced vocalizations in social settings, and high levels of repetitive self-grooming. Autism-relevant phenotypes in BTBR offer translational tools to discover neurochemical mechanisms underlying unusual mouse behaviors relevant to symptoms of autism. Because repetitive self-grooming in mice may be a displacement behavior elevated by stressors, we investigated neuroendocrine markers of stress and behavioral reactivity to stressors in BTBR mice, as compared to C57BL/6J (B6), a standard inbred strain with high sociability. Radioimmunoassays replicated previous findings that circulating corticosterone is higher in BTBR than in B6. Higher basal glucocorticoid receptor mRNA and higher oxytocin peptide levels were detected in the brains of BTBR as compared to B6. No significant differences were detected in corticotrophin releasing factor (CRF) peptide or CRF mRNA. In response to behavioral stressors, BTBR and B6 were generally similar on behavioral tasks including stress-induced hyperthermia, elevated plus-maze, light ↔ dark exploration, tail flick, acoustic startle and prepulse inhibition. BTBR displayed less reactivity than B6 to a noxious thermal stimulus in the hot plate, and less immobility than B6 in both the forced swim and tail suspension depression-related tasks. BTBR, therefore, exhibited lower depression-like scores than B6 on two standard tests sensitive to antidepressants, did not differ from B6 on two well-validated anxiety-like behaviors, and did not exhibit unusual stress reactivity to sensory stimuli. Our findings support the interpretation that autism-relevant social deficits, vocalizations, and repetitive behaviors are not the result of abnormal stress reactivity in the BTBR mouse model of autism.

KW - Autism

KW - BTBR

KW - Mouse models

UR - http://www.scopus.com/inward/record.url?scp=78650176892&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650176892&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2010.09.059

DO - 10.1016/j.neuroscience.2010.09.059

M3 - Article

C2 - 20888890

AN - SCOPUS:78650176892

VL - 171

SP - 1197

EP - 1208

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 4

ER -