Abstract 277: Development of Anxiety- and Depression-Like Behavior in Mice After Myocardial Infarction

Objective: Anxiety and depression are common and independently predict mortality in patients with heart failure. The mechanisms of these interrelations are still unclear. Consequently, we developed a model in C57BL/6 mice with experimental myocardial infarction (MI) and heart failure to study anxiety- or depression-like behavior. Methods: Heart failure was achieved after coronary artery ligation in 13 mice; 16 sham operated mice acted as controls. Left ventricular (LV) remodeling was assessed by echocardiography, infarct size by histology. Sucrose preference test was performed over a period of 8 weeks to assess depression-like behavior. The elevated plus maze (EPM), the light-dark box (LDB) and the open field (OF) tests were subsequently applied to determine general disinterest and anxiety-like behavior. Finally, the histological and immunohistochemical evaluation of the brain was performed. Results: Mice with MI size of at least 30% of LV (averaged 50±3%; increase in diastolic LV diameter from 0.40±0.02 cm to 0.62±0.03 cm) showed diminished intake (p=0.029) and preference (p=0.029) for sucrose solution. Besides, MI mice exhibited reduced exploratory behavior and markedly lower interest in unfamiliar environments, indicated by an increase in center time (p=0.016) and a reduced number of vertical rears (p=0.037) in the EPM. An increased latency to the first rear (p=0.018), covered shorter distances (p=0.048) and spent less time moving (p=0.028) in the OF were found in MI mice. MI did not affect anxiety-related measures in all three tests (all p>0.05). MI mice showed normal brain morphology with normal neuronal morphology and neuropil structure, also confirmed by normal expression of selected neuronal markers. Markers for neurodegeneration, apoptosis or inflammation showed no abnormalities in MI mice. Conclusions: Mice with MI exhibited anhedonia-like behavior, which was accompanied by other characteristics of depression-like behavior, such as decreased exploratory activity and interest in novelty. Hence, MI caused distinct behavioral changes in mice comparable to symptoms observed in humans with heart failure and comorbid depression, but did not affect anxiety-like behavior. The model is suitable for further mechanistic studies.