The purpose of the Animal Core is to provide a consistent, uniform, and reliable source of animals instrumented and trained in cocaine self-administration for use in all of the projects of the NARC. Rats wlll be catheterized and trained to self-administer intravenous cocaine using a standardized and clinically relevant experimental paradigm. Subjects will then be directed towards individual NARC projects for brain tissue extraction, electrophysiology, or assessment of behavioral responding to systemic or site directed manipulations in accordance with the specific aims of each NARC project. The animal core in this renewal will expand to incorporate a transgenic TH::Cre rat colony that will provide transgenic rats to NARC projects with opsins expressed selectively in dopamine neurons. As part of providing optogenetic support for projects using TH:Cre rats, the Animal Core supports an optogenetics core containing the necessary equipment and expertise to allow all NARC optogenetic studies to proceed in a synergistic and competent manner. The primary objectives of the Animal Core core are: 1. Provide rats to all projects that satisfy specific criteria regarding experience in drug self-administration, and in the degree of withdrawal, extinction, and/or abstinence, as well as regarding intracranial injections of viral vectors. 2. Manage the distribution of rats to projects to insure that statistically relevant group sizes and group replications are made available to each project in a timely manner. 3. Provide trained technicians to efficiently generate experimental subjects using a balanced group design. 4. Maintain a colony of TH::Cre rats individually validated for Cre expression and provide the numbers of identified Cre+ and Cre- rats required across NARC projects. 5. Serve as a NARC training center for MUSC and offsite investigators who desire training in self- administration, jugular catheterization, operant conditioning methods, viral vector design, viral vector microinjections, optogenetic practices, and other related experimental procedures. 6. Provide the equipment, resources, and personnel for using optogenetics to manipulate specific neurons as appropriate across NARC projects. This includes maintaining a supply of virus expressing the various opsin transgenes needed by the NARC projects.
Since the NARC was established, the Animal Core has been a highly effective resource for projects and pilot projects by providing 1) a reliable and consistent source of operantly-trained animals and 2) mentoring and education. It will continue this role in the renewal and also incorporate a core facility for breeding and distributing TH::Cre rats and providing optogenetics training and testing. Thus, the Animal Core will continue and expand its role as the integrative experimental center that brings strong synergy to the NARC projects.
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