Now that we are beginning to mechanistically explore this system using well defined cell models, we will be able to ask more specific questions in in vivo systems relating to disease states. Such regulation selleck products may suggest new ideas about treatment and prevention of diseases associated with extreme hormonal fluctuations such as in postpar tum depression. Background Stress is a potent risk factor in the development of mood and anxiety disorders and other psychopatholo gies. For example, stress is an important non genetic cause of major depressive disorder, with both acute Inhibitors,Modulators,Libraries and chronic forms capable of precipitating major depressive episodes.

A number of theories have been proposed to explain how stress alters brain Inhibitors,Modulators,Libraries struc ture and function in stress responsive areas and there is compelling evidence for synaptic plasticity dys regulation, with much work having elucidated how the glucocorticoid and various neurotransmitter systems contribute to this dysregulation. In order to better understand how stress affects brain function, we have previously used a chronic psycho logical stress model and found that this stress para digm markedly upregulates deltaFosB expression, a marker of ongoing neuronal activity, in the Inhibitors,Modulators,Libraries infralimbic medial prefrontal cortex. The ILmPFC is implicated in processing emotional Inhibitors,Modulators,Libraries context and, con sistent with this notion, human patients with vmPFC lesions showed impaired social emotions. Add itionally, deep brain stimulation of the vmPFC region can prolong remission of depression in treatment resistant patients, indicating a role for this brain region in depressive states.

These human data and our previous findings using chronic psychological stress, which is known to increase vulnerability to the devel opment of depression like symptoms, led us to initially focus on the ILmPFC to better understand the neurobiology of stress and how this might potentially lead to depression sequelae. To identify as Inhibitors,Modulators,Libraries many ILmPFC mechanisms as possible that are involved in the response to repeated stress, we used a genome wide, gene expression analysis ap proach. We also chose a restraint stress model as this type of psychological stress affords greater control in application of the stressor than with, for example, the social conflict model.

As selleck kinase inhibitor the neural correlates that underpin the transition to the depressive state are not understood, we tried to identify early stress induced changes that may increase susceptibility to the develop ment of a full depression like state. It is known that multiple stress experiences are generally needed to cause MDD in humans and are absolutely required to develop depression like symptoms in animals, so we used what can be considered a sub chronic stress para digm that does not lead to these behavioural symptoms.