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


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.
Truitt
William A
WA
Department of Psychiatry, Indiana University School of Medicine, 1111 West 10th Street, Indianapolis, IN 4620, USA.
Sajdyk
Tammy J
TJ
Dietrich
Amy D
AD
Oberlin
Brandon
B
McDougle
Christopher J
CJ
Shekhar
Anantha
A
D000679:Amygdala / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology*; D001321:Autistic Disorder / Q000503:physiopathology / Q000523:psychology*; D001522:Behavior, Animal; D003346:Corticotropin-Releasing Hormone; D004195:Disease Models, Animal; D006185:Habituation, Psychophysiologic; D007395:Interneurons / Q000378:metabolism; D008297:Male; D009433:Neural Inhibition; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012919:Social Behavior; D012920:Social Behavior Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D013997:Time Factors; D054832:Urocortins
D018019:Receptors, Corticotropin-Releasing Hormone; D018040:Receptors, Neurokinin-1; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C454685:SSP-SAP fusion protein, recombinant; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D000076985:Saporins