@article{FreyPoppPostetal.2014, author = {Frey, Anna and Popp, Sandy and Post, Antonia and Langer, Simon and Lehmann, Marc and Hofmann, Ulrich and Siren, Anna-Leena and Hommers, Leif and Schmitt, Angelika and Strekalova, Tatyana and Ertl, Georg and Lesch, Klaus-Peter and Frantz, Stefan}, title = {Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain}, series = {Frontiers in Behavioral Neuroscience}, volume = {8}, journal = {Frontiers in Behavioral Neuroscience}, issn = {1662-5153}, doi = {10.3389/fnbeh.2014.00376}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118234}, pages = {376}, year = {2014}, abstract = {Background: Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI). Methods and Results: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM), light-dark box (LDB), open field (OF), and object recognition (OR) tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI. Conclusions: After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.}, language = {en} } @article{KlokeSchreiberBoddenetal.2014, author = {Kloke, Vanessa and Schreiber, Rebecca S. and Bodden, Carina and M{\"o}llers, Julian and Ruhmann, Hanna and Kaiser, Sylvia and Lesch, Klaus-Peter and Sachser, Norbert and Lewejohann, Lars}, title = {Hope for the Best or Prepare for the Worst? Towards a Spatial Cognitive Bias Test for Mice}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {8}, doi = {10.1371/journal.pone.0105431}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115569}, pages = {e105431}, year = {2014}, abstract = {Cognitive bias, the altered information processing resulting from the background emotional state of an individual, has been suggested as a promising new indicator of animal emotion. Comparable to anxious or depressed humans, animals in a putatively negative emotional state are more likely to judge an ambiguous stimulus as if it predicts a negative event, than those in positive states. The present study aimed to establish a cognitive bias test for mice based on a spatial judgment task and to apply it in a pilot study to serotonin transporter (5-HTT) knockout mice, a well-established mouse model for the study of anxiety- and depression-related behavior. In a first step, we validated that our setup can assess different expectations about the outcome of an ambiguous stimulus: mice having learned to expect something positive within a maze differed significantly in their behavior towards an unfamiliar location than animals having learned to expect something negative. In a second step, the use of spatial location as a discriminatory stimulus was confirmed by showing that mice interpret an ambiguous stimulus depending on its spatial location, with a position exactly midway between a positive and a negative reference point provoking the highest level of ambiguity. Finally, the anxiety- and depression-like phenotype of the 5-HTT knockout mouse model manifested - comparable to human conditions - in a trend for a negatively distorted interpretation of ambiguous information, albeit this effect was not statistically significant. The results suggest that the present cognitive bias test provides a useful basis to study the emotional state in mice, which may not only increase the translational value of animal models in the study of human affective disorders, but which is also a central objective of animal welfare research.}, language = {en} }