Transgene expression studies

Upregulation of CREB could play an important role in the actions of antidepressant treatment. To directly test this hypothesis, the influence of CREB expression in models of depression has been examined. For these studies, the expression of CREB or a dominant-negative mutant of CREB (mCREB) is increased by viral mediated gene transfer or by inducible transgenic expression. In addition, the influence of null mutation of one isoform, a-CREB, on behavior has been studied. Viral expression of wild-type CREB in the hippocampus, where antidepressant treatment increases CREB, results in an antidepressantlike effect in the forced swim (FST) and learned helplessness (LH) paradigms (Chen et al. 2001). The results demonstrate that increased expression of CREB is sufficient to produce an antidepressant effect and support the hypothesis that this transcription factor is an important target of antidepressant treatment. 

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