The biochemical core primary objectives are to develop and provide viral vectors for the overexpression of neuropeptides or for the delivery of antisense sequences to such peptides or their receptors, and to synthesize and measure neurosteroids for investigators in the TSRI-ARC and Center at Large. The viral vector Component will serve as a service unit for the development and production of viral vectors for investigators in the TSRI-ARC and Center at Large. The core will generate the vector constructs, package and expand the vectors, and evaluate vector gene transduction efficiency and levels of expression. The use of viral vectors is of interest to the ARC components directed by Drs. Rivier, Weiss, and Zorrilla (pilot), as well as for Dr. Ehlers and Dr. Koob NIAAA-supported research. All these investigators plan to use viral vectors for the modulation (up/down-regulation) of the expression of the neuropeptides NPY, CRF and their receptors. The centralization of these activities in the present core will allow for the systematic characterization of the most advantageous vector/promoter combinations for transgene delivery and expression in brain regions relevant to alcohol's actions and for the cost-effective and efficient production of such vectors. The neurosteroid component serves as a service unit for the synthesis and measurement of neuroactive steroids for investigators in the TSRI-ARC and Center at Large. Neuroactive steroids are potent neuromodulators, some of which (termed neurosteroids) are synthesized by the nervous system from cholesterol or derived from metabolites of steroid hormones of endocrine gland origin, such as progesterone or deoxycorticosterone. The primary objectives of this component will be to synthesize and purify neurosteroids for use by TSRI-ARC and Center at Large investigators, including Drs. Craig Slawecki, Friedbert Weiss, George Siggins, and Karen Britton. This component will also coordinate the tissue collection, processing, and measurement of neurosteroids by GC/MS in alcohol-related investigations at TSRI; and develop new syntheses for neurosteroid derivatives that interact with GABAA-receptors and NMDA-receptors involved in alcohol preference in alcohol-dependent animals provided by the Animal Core.
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