The ability to expose experimental rodents to alcohol over periods of hours to days is crucial to research. At present, the methods used to do so include repeated injections, feeding the animals a liquid diet containing alcohol, or group-housing them in large chambers through which alcohol vapors are circulated. The disadvantages of these methods include the presence of a stressful procedure, an inadequate diet and/or the inability to access individual animals while they are in the vapor environment. Under Phase I, we developed a prototype that showed the feasibility of building individual rat cages through which we could circulate known amount of alcohol vapors. This system allowed us to develop charts which correlated blood alcohol levels (BALs) to pre-determined parameters of alcohol delivery. Phase II will expand the scientific ideas successfully explored under Phase I. As investigators use different rat strains, both males and females, and want to treat their animals for several days, we will develop charts for male and female (both virgin and pregnant) Sprague-Dawley, Wistar and Long-Evans rats. This is necessary because alcohol metabolism varies between strains and genders, and changes during pregnancy. Consequently we cannot assume that the charts developed under Phase I are applicable to other models. We will also modify the existing rat prototype so that the chambers can accommodate food holders and water bottles, as well as outlets for cannulae, while the integrity of the system is maintained during long-term housing. A stand holding syringes and/or the recording instruments will be built, that fits over the chambers. Finally, we found that mice housed in rat chambers had very heterogeneous BALs. Therefore an important aspect of our work will consist in building chambers for mice, a species that is increasingly used in alcohol research, but which will require a redesign of the system to accommodate their smaller size. Once this new design has been determined, we will develop charts correlating parameters of alcohol delivery to target BALs in mice of three commonly used strains, BALB/c, C57BL/6 and DBA/2. The finished rat and mouse products will represent a very significant improvement over presently available systems. It will be versatile, user-friendly and affordable. While originally designed for alcohol work, we anticipate that it will be easily modifiable for other volatile, non-corrosive substances, including those that are presently difficult to study because they are highly toxic.
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Gilpin, Nicholas W; Smith, Amanda D; Cole, Maury et al. (2009) Operant behavior and alcohol levels in blood and brain of alcohol-dependent rats. Alcohol Clin Exp Res 33:2113-23 |