From anxiety to autism: Spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats

William Truitt, Tammy J. Sajdyk, Amy D. Dietrich, Brandon Oberlin, Christopher J. McDougle, Anantha Shekhar

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Rationale: Social behaviors are disrupted in several psychiatric disorders. The amygdala is a key brain region involved in social behaviors, and amygdala pathology has been implicated in disease states ranging from social anxiety disorder to autism. Objective: To test the effects of progressive disruption of the inhibitory function within the basolateral nucleus of the amygdala (BLA) on conspecific social interaction in rats and investigate functional networks from the ventral medial prefrontal cortex (mPFCv) to the BLA. Materials and methods: BLA inhibitory tone was disrupted by priming it with the stress-peptide corticotrophin releasing factor (CRF) receptor agonist urocortin 1 (Ucn 1, 6 fmol), or by selective lesioning of a subset of BLA-GABAergic interneurons containing neurokinin 1 receptors using the targeted toxin SSP-Saporin. The effects of the disruption of GABAergic tone in the BLA were examined using a repeated exposure and habituation paradigm of social interaction (SI/h). Lesions and selectivity of lesions were confirmed postmortem. Additionally, effects of stimulating mPFCv on cFos activity in interneurons of the BLA were examined. Results: Rats primed with Ucn 1 showed persistent social inhibition, which could be overcome with habituation, putatively modeling social anxiety. Rats with a selective lesioning of a subset of GABAergic interneurons in the BLA exhibited persistent social inhibition that was not reversed by SI/h paradigm. We also demonstrate selective functional inputs to this subset of interneurons when mPFCv was activated. Conclusions: These models with different gradations of disrupted BLA inhibition could help to study social dysfunction in disorders ranging from social anxiety to autism spectrum disorders.

Original languageEnglish
Pages (from-to)107-118
Number of pages12
JournalPsychopharmacology
Volume191
Issue number1
DOIs
StatePublished - Mar 2007

Fingerprint

Social Behavior
Autistic Disorder
Amygdala
Wistar Rats
Anxiety
Interneurons
Interpersonal Relations
Urocortins
Basolateral Nuclear Complex
Corticotropin-Releasing Hormone Receptors
Neurokinin-1 Receptors
Immunotoxins
Prefrontal Cortex
Psychiatry
Pathology
Peptides

Keywords

  • Basolateral amygdala
  • Depression
  • Interneuron
  • Negative symptoms
  • Pervasive developmental disorders
  • Schizophrenia
  • Social anxiety

ASJC Scopus subject areas

  • Pharmacology

Cite this

From anxiety to autism : Spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats. / Truitt, William; Sajdyk, Tammy J.; Dietrich, Amy D.; Oberlin, Brandon; McDougle, Christopher J.; Shekhar, Anantha.

In: Psychopharmacology, Vol. 191, No. 1, 03.2007, p. 107-118.

Research output: Contribution to journalArticle

@article{acb1dfe2fb6b4a6684ee67a6aa656aab,
title = "From anxiety to autism: Spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats",
abstract = "Rationale: Social behaviors are disrupted in several psychiatric disorders. The amygdala is a key brain region involved in social behaviors, and amygdala pathology has been implicated in disease states ranging from social anxiety disorder to autism. Objective: To test the effects of progressive disruption of the inhibitory function within the basolateral nucleus of the amygdala (BLA) on conspecific social interaction in rats and investigate functional networks from the ventral medial prefrontal cortex (mPFCv) to the BLA. Materials and methods: BLA inhibitory tone was disrupted by priming it with the stress-peptide corticotrophin releasing factor (CRF) receptor agonist urocortin 1 (Ucn 1, 6 fmol), or by selective lesioning of a subset of BLA-GABAergic interneurons containing neurokinin 1 receptors using the targeted toxin SSP-Saporin. The effects of the disruption of GABAergic tone in the BLA were examined using a repeated exposure and habituation paradigm of social interaction (SI/h). Lesions and selectivity of lesions were confirmed postmortem. Additionally, effects of stimulating mPFCv on cFos activity in interneurons of the BLA were examined. Results: Rats primed with Ucn 1 showed persistent social inhibition, which could be overcome with habituation, putatively modeling social anxiety. Rats with a selective lesioning of a subset of GABAergic interneurons in the BLA exhibited persistent social inhibition that was not reversed by SI/h paradigm. We also demonstrate selective functional inputs to this subset of interneurons when mPFCv was activated. Conclusions: These models with different gradations of disrupted BLA inhibition could help to study social dysfunction in disorders ranging from social anxiety to autism spectrum disorders.",
keywords = "Basolateral amygdala, Depression, Interneuron, Negative symptoms, Pervasive developmental disorders, Schizophrenia, Social anxiety",
author = "William Truitt and Sajdyk, {Tammy J.} and Dietrich, {Amy D.} and Brandon Oberlin and McDougle, {Christopher J.} and Anantha Shekhar",
year = "2007",
month = "3",
doi = "10.1007/s00213-006-0674-y",
language = "English",
volume = "191",
pages = "107--118",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - From anxiety to autism

T2 - Spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats

AU - Truitt, William

AU - Sajdyk, Tammy J.

AU - Dietrich, Amy D.

AU - Oberlin, Brandon

AU - McDougle, Christopher J.

AU - Shekhar, Anantha

PY - 2007/3

Y1 - 2007/3

N2 - Rationale: Social behaviors are disrupted in several psychiatric disorders. The amygdala is a key brain region involved in social behaviors, and amygdala pathology has been implicated in disease states ranging from social anxiety disorder to autism. Objective: To test the effects of progressive disruption of the inhibitory function within the basolateral nucleus of the amygdala (BLA) on conspecific social interaction in rats and investigate functional networks from the ventral medial prefrontal cortex (mPFCv) to the BLA. Materials and methods: BLA inhibitory tone was disrupted by priming it with the stress-peptide corticotrophin releasing factor (CRF) receptor agonist urocortin 1 (Ucn 1, 6 fmol), or by selective lesioning of a subset of BLA-GABAergic interneurons containing neurokinin 1 receptors using the targeted toxin SSP-Saporin. The effects of the disruption of GABAergic tone in the BLA were examined using a repeated exposure and habituation paradigm of social interaction (SI/h). Lesions and selectivity of lesions were confirmed postmortem. Additionally, effects of stimulating mPFCv on cFos activity in interneurons of the BLA were examined. Results: Rats primed with Ucn 1 showed persistent social inhibition, which could be overcome with habituation, putatively modeling social anxiety. Rats with a selective lesioning of a subset of GABAergic interneurons in the BLA exhibited persistent social inhibition that was not reversed by SI/h paradigm. We also demonstrate selective functional inputs to this subset of interneurons when mPFCv was activated. Conclusions: These models with different gradations of disrupted BLA inhibition could help to study social dysfunction in disorders ranging from social anxiety to autism spectrum disorders.

AB - Rationale: Social behaviors are disrupted in several psychiatric disorders. The amygdala is a key brain region involved in social behaviors, and amygdala pathology has been implicated in disease states ranging from social anxiety disorder to autism. Objective: To test the effects of progressive disruption of the inhibitory function within the basolateral nucleus of the amygdala (BLA) on conspecific social interaction in rats and investigate functional networks from the ventral medial prefrontal cortex (mPFCv) to the BLA. Materials and methods: BLA inhibitory tone was disrupted by priming it with the stress-peptide corticotrophin releasing factor (CRF) receptor agonist urocortin 1 (Ucn 1, 6 fmol), or by selective lesioning of a subset of BLA-GABAergic interneurons containing neurokinin 1 receptors using the targeted toxin SSP-Saporin. The effects of the disruption of GABAergic tone in the BLA were examined using a repeated exposure and habituation paradigm of social interaction (SI/h). Lesions and selectivity of lesions were confirmed postmortem. Additionally, effects of stimulating mPFCv on cFos activity in interneurons of the BLA were examined. Results: Rats primed with Ucn 1 showed persistent social inhibition, which could be overcome with habituation, putatively modeling social anxiety. Rats with a selective lesioning of a subset of GABAergic interneurons in the BLA exhibited persistent social inhibition that was not reversed by SI/h paradigm. We also demonstrate selective functional inputs to this subset of interneurons when mPFCv was activated. Conclusions: These models with different gradations of disrupted BLA inhibition could help to study social dysfunction in disorders ranging from social anxiety to autism spectrum disorders.

KW - Basolateral amygdala

KW - Depression

KW - Interneuron

KW - Negative symptoms

KW - Pervasive developmental disorders

KW - Schizophrenia

KW - Social anxiety

UR - http://www.scopus.com/inward/record.url?scp=33847106367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847106367&partnerID=8YFLogxK

U2 - 10.1007/s00213-006-0674-y

DO - 10.1007/s00213-006-0674-y

M3 - Article

C2 - 17277936

AN - SCOPUS:33847106367

VL - 191

SP - 107

EP - 118

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 1

ER -