Premium
Rats with ischemic heart failure (IHF) exhibit exaggerated conditioned fear and altered β‐adrenergic receptor expression in forebrain regions that govern autonomic responses to fear
Author(s) -
Glasgow Jaimee,
Cunha Jonathan,
Tiniakov Ruslan,
Samarel Allen,
Koshman Yevgeniya,
Neafsey Edward J,
Battaglia George,
Scrogin Karie
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.703.19
Subject(s) - forebrain , medicine , endocrinology , infralimbic cortex , basolateral amygdala , agonist , receptor , adrenergic , prefrontal cortex , stimulation , extinction (optical mineralogy) , amygdala , neuroscience , chemistry , psychology , central nervous system , cognition , mineralogy
Up to 26% of patients with IHF develop anxiety disorders. β‐adrenergic receptors (βARs) in the basolateral amygdala (BLA) mediate fear expression, while βARs in the infralimbic region of the medial prefrontal cortex (IL) contribute to extinction of learned fear. We found that stimulation of the locus ceoruleus (the main source of adrenergic input to the forebrain) reduced metabolic activity in the IL and increased arrhythmias in IHF rats, but not in controls. Here, we determined if rats with IHF exhibit increased conditioned fear, deficits in fear extinction and altered βAR receptor density in the forebrain. Rats trained to associate foot shock (0.5 mA, 0.5 s) with a 10 s tone were subjected to coronary artery ligation or sham surgery. Rats with IHF (fractional shortening < 25%) showed increased freezing behavior during the first 3 extinction tones (3.2±0.6 vs 6.2±0.5 s, P <0.05), and delayed fear extinction (4.1±0.7 vs 10.5±1.3 trials, P <0.01) compared to controls 7 weeks after surgery. β 1 AR density was reduced in the IL (15%) and rostral BLA (29%) of IHF rats ( P <0.05). Inhibition of βAR antagonist binding by a βAR agonist was increased two‐fold in the BLA of IHF rats ( P <0.05), suggesting a greater density of G protein‐coupled βAR receptors. These data implicate altered forebrain adrenergic neurotransmission in the anxiety and increased arrhythmias that develop with IHF. Supported by AHA 09PRE2260787.