In addition, we have found that chronic rolipram
administration increases neurogenesis in adult hippocampus.46,58 Second, viral expression of CREB in the hippocampus of rat produces an antidepressant response in the forced swim and learned helplessness models of depression.59 However, further studies demonstrated that the effects of CREB are dependent on the brain region where it is expressed. For example, expression of CREB in the nucleus accumbens produces a prodepressant effect, while expression of a dominant, Inhibitors,research,lifescience,medical negative mutant of CREB results in an antidepressant response in the forced swim test.60 Transgenic expression of dominant negative CREB in the nucleus accumbens is consistent with this effect.61 The different behavioral effects of CREB can be explained by different target genes in the hippocampus (ic, BDNF) versus the nucleus accumbens (ie,prodynorphin). Regulation of neurotrophic factors Inhibitors,research,lifescience,medical and depression The regulation of CREB by antidepressant treatment indicates that regulation of gene expression also plays a role in the actions of antidepressants. There have been many gene targets identified for antidepressants,51,52 but BDNF is one that has gained attention and is relevant to neural plasticity responses to Inhibitors,research,lifescience,medical antidepressant medications. Studies to identify additional gene targets and gene profiles using gene microarray analysis are currently being conducted. Antidepressant treatment upregulates BDNF Neurotrophic
factors were originally
identified and studied for their role in development, and neuronal survival. However, it is now clear that these factors are expressed in the adult brain, arc dynamically regulated by neuronal activity, and are Inhibitors,research,lifescience,medical critical for the survival and function of adult neurons. On the basis of these considerations, it is clear why decreased expression of BDNF could have serious consequences for the function of limbic brain Inhibitors,research,lifescience,medical structures that control mood and cognition. In contrast, antidepressant treatment results in significant upregulation of BDNF in the hippocampus and cerebral cortex of rodents.28,53,54 Increased expression of BDNF is dependent on chronic treatment, and is Antidiabetic Compound Library high throughput observed with different classes of antidepressants, but not other psychotropic drugs. The induction of BDNF would be expected to protect neurons from damage resulting from stress, elevated glucocorticoids, or other types of neuronal insult. BDNF has antidepressant effects in behavioral models of depression many The possibility that BDNF contributes to the actions of antidepressant treatment is supported by behavioral studies of recombinant BDNF and transgenic mouse models. Microinfusions of BDNF into the hippocampus produce an antidepressant-like response in the learned helplessness and forced swim models of depression.62 The antidepressant, effect of BDNF is observed after a single infusion, compared with repeated administration of a. chemical antidepressant, and is relatively long-lasting (up to 10 days after infusion).