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

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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 (US)
Pages (from-to)107-118
Number of pages12
JournalPsychopharmacology
Volume191
Issue number1
DOIs
StatePublished - Mar 1 2007

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Keywords

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

ASJC Scopus subject areas

  • Pharmacology

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