title: Myocardial infarction sensitizes medial prefrontal cortex to inhibitory effect of locus coeruleus stimulation in rats.
abstract: Anxiety is a common comorbidity that develops after myocardial infarction and is now an established independent risk factor for cardiovascular mortality.
  
  
  
  Here, we assessed anxiety and mapped neural activity of forebrain regions that regulate anxiety in a rat model of myocardial infarction in order to identify sites of dysregulation.
  
  
  
  Anxiety responses to novel (open field) or aversive stimuli (discriminative auditory fear conditioning) were assessed in rats subjected to coronary artery ligation (CAL) or sham ligation. Forebrain metabolic activity was measured by cytochrome oxidase (CO) histochemistry. Changes in CO activity and the incidence of ventricular arrhythmias were also assessed during modulation of fear circuitry induced by electrical stimulation of the locus coeruleus.
  
  
  
  Coronary artery ligation had negligible effects on open-field behavior, but increased expression of learned fear and impaired fear cue discrimination. Cytochrome oxidase activity was increased in the medial prefrontal cortex and in the lateral amygdala after CAL. Locus coeruleus stimulation reduced CO activity in the infralimbic medial prefrontal cortex only in rats subjected to CAL. Stimulation of the LC also elicited new ventricular arrhythmias in rats subjected to CAL.
  
  
  
  Coronary artery ligation sensitizes the infralimbic medial prefrontal cortex to the inhibitory effects of locus coeruleus stimulation. Suppression of infralimbic medial prefrontal cortical activity may impair the ability of rats subjected to CAL to discriminate between cues that signal aversive and neutral events which, in turn, may promote excessive sympathetic activation of the cardiovascular system in response to innocuous stimuli.
authors.affiliation: Graduate Program in Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
authors.forename: Jaimee
authors.initials: J
authors.lastname: Glasgow
authors.affiliation: Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Koshman
authors.affiliation: Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
authors.forename: Allen M
authors.initials: AM
authors.lastname: Samarel
authors.affiliation: Department of Cellular and Molecular Pharmacology, The Chicago Medical School at Rosalind Franklin University, North Chicago, IL, USA.
authors.forename: Kuei Y
authors.initials: KY
authors.lastname: Tseng
authors.affiliation: Graduate Program in Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA. kscrogi@luc.edu.|Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA. kscrogi@luc.edu.|Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA. kscrogi@luc.edu.
authors.forename: Karie
authors.initials: K
authors.lastname: Scrogin
mesh_terms: D000679:Amygdala / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D003576:Electron Transport Complex IV / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D007266:Inhibition, Psychological; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003576:Electron Transport Complex IV
keywords: Amygdala; Anxiety; Arrhythmia; Blood pressure; Cytochrome oxidase; Fear conditioning