This approach bypasses several biases introduced by overexpressing the wild-type GR and submitting the animals to an actual stress. Thus in the latter case glucocorticoids levels need to be increased to activate the overexpressed wild-type GR. It will then be impossible to eliminate the influence of: 1. GRindependent effects of glucocorticoids; 2. Transcription-independent 
effects of GC-activated GR; 3 The effects mediated by the activation of the endogenous GR in other cellular types. In this report we used a transgenic approach that allows expression of the DGR prevalently in glutamatergic neurons of the dentate gyrus of the hippocampus. In these mutant animals DGR overexpression was stably induced at five months of age. These animal models then mimic the effects of certain forms of chronic stress specifically in this neuronal population in which the circadian secretion of glucocorticoids is lost and glucocorticoid levels are permanently high. In these animals we investigated anxiety-related behaviors, using the elevated plus maze and the emergence test. We also analyzed other GR-mediated behaviors that might indirectly modify performances in anxiety tests. We also studied the MAPK signaling pathway and the downstream MAPK-regulated protein Egr-1 since in the hippocampus they are regulated by the GR. However, in animal models anxiety and Atropine sulfate depression are not two dimensions that can be easily separated and most tests actually screen different forms of behavioral Gentamycin Sulfate responses to unavoidable aversive situations. In the forced swim test, mice are forced to swim in a small transparent cylinder. After unsuccessful attempts to escape, mice stop swimming and float. We measured both the latency and the duration of immobility as a measure of despair. The time spent in novel open areas, usually used to measure anxiety, results from the computation of two opposite motivational forces. The fear of potential threats driving avoidance, and novelty-seeking driving exploration. Consequently, a decrease in the time spent in the open arms of the EPM or an increase in the latency in exiting the protective cylinder in the emergence test could result from either an increase in the fear of potential threats or a decrease in novelty exploration. In order to address this issue, we evaluated Eno2-DGR/EGFP bigenic mice for the exploration of a novel object in a non-threatening environment. For this test animals are first habituated to the test apparatus in the absence of the object in order to diminish the fear component of exposure to an unknown environment. It is noteworthy that the forced swim test has also been linked to depression and is largely used to screen for antidepressants. Several data indicate that anxiety disorders share common symptoms with depression and anxiety and depression frequently coexist. Furthermore, most antidepressants also have anxiolytic effects. This is probably why overexpression of the DGR in a specific cellular target modified both prototypical anxiety-related behaviors and the forced swim test. This variability in transgene expression is caused mainly by the stochastic event of transgene integration within the host genome and the nature of the transgenic constructs. It is well accepted that host sequences surrounding the site of transgene integration but also transgene copy numbers, methylation at the transgene locus and heterochromatin-induced position effect variegation can modify the expected expression pattern, potentially causing it to be ectopic, weak, delayed or even undetectable. This is currently interpreted as the result of chromosomal position effects.