After myocardial infarction (MI), rats display neophobia and altered forebrain metabolic activation in response to locus coeruleus (LC) stimulation

Up to 45% of patients develop depression or anxiety after MI, and such patients show increased morbidity and mortality. Studies suggest that the central noradrenergic system is overactive in depression and anxiety. The basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) receive adrenergic input and control behavioral and autonomic responses to stress. Here, we determined if rats subjected to coronary artery ligation (CAL) exhibited increased anxiety‐like behavior in an open field and altered metabolic activation in the BLA and mPFC during LC stimulation under chloral hydrate anesthesia. Seven wks after surgery CAL rats had decreased left ventricular fractional shortening (P<0.01) and increased lung‐ and heart‐to‐tibia length ratios (P<0.01) vs. rats subjected to sham ligation. In the Open Field test, CAL rats took longer to leave the center square than shams (P<0.05), suggesting enhanced neophobia. Eight wks after surgery, CAL rats had increased baseline metabolic activity in the mPFC (P<0.01), as assessed by cytochrome oxidase activity (COA). Twenty min of electrical stimulation of the LC in a pattern designed to simulate mild stress decreased COA in the mPFC of CAL rats, but not shams (CAL × stimulation, P<0.01). CAL rats exhibited decreased baseline COA in the rostral BLA (P<0.05). More caudally, COA was decreased in the lateral nucleus of the amygdala in CAL rats (P<0.05). Funded by AHA 09PRE2260787