Role of central VIP in stress regulation

Stress-associated diseases such as depression and anxiety disorders are the most common cause of psychiatric illness. In addition to the enormous burden on the social and health systems, these diseases lead to considerable suffering and a reduction in the quality of life of those affected. Unfortunately, currently available drug treatments do not offer sufficient and satisfactory therapeutic efficacy, since many patients do not respond to them in the desired manner or there are sometimes considerable side effects. The identification of neurobiological mechanisms that underlie stress-associated diseases such as depression is the basis for new, improved therapeutic approaches. Research in recent years has shown that neuropeptide systems play an important role in regulating stress and anxiety reactions. For example, there is evidence that the neuropeptide vasoactives-intestinal peptide (VIP) is associated with diseases such as schizophrenia and bipolar disorders, since gene polymorphisms within the gene encoding VIP could be associated with abnormal stress reactions in these diseases. The main goal of the present project is therefore to elucidat e in an animal model the role of VIP and its receptors (VPAC1 and 2 receptor) in the regulation of stress and anxiety reactions. In particular, we will identify distinct brain structures in which stress-induced changes in the VIP/VPAC receptor system can be functionally associated with a changed physiological and behavioral stress response. Moreover, possible correlations of individual differences in stress susceptibility with changes in VIP neurotransmission will also be examined. In addition to the characterization of stress-induced changes in the VIP/VPAC receptor system in various brain structures, we will investigate whether a selective activation or inhibition of distinct VIP pathways modulates the stress reactivity. Thus, the results of this project should contribute to a better understanding of the functional role of central VIP in stress mechanisms. This knowledge is of considerable value for the recent proposed role of the VIP/VPAC receptor system as a therapeutic target in the treatment of stress-related psychiatric diseases.