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ISBRA 2004 Abstracts
Oregon Health and Science University, Portland, OR
MODIFIED FLUID RESTRICTION PARADIGM DETECTS GENETIC DIFFERENCES IN HIGH ETHANOL INTAKE
D.A. Finn; N. Yoneyama; A.R. Wetzel; J.C. Crabbe
VAMC Research, Portland Alcohol Research Center & Dept. of Behavioral Neuroscience, OHSU, Portland, OR 97239 USA
Recent work in our laboratory found that scheduling periods of fluid availability produced high, stable ethanol (EtOH) intake (³ 2 g/kg in 30 min) and ataxia in an inbred strain that exhibits preference (C57BL/6; B6) and in genetically heterogeneous mice. Thus, the purpose of the present experiments was to test genotypes, which differ in voluntary EtOH intake, on our modified fluid restriction paradigm. B6, DBA/2 (D2), B6D2F2, and mice selectively bred for high (STDRHI) and low (STDRLO) voluntary EtOH intake received a total of 7 EtOH sessions (5% solution, 30 min) every 3rd day. Mice initially had 4 hrs of fluid/day for the 1st 3 EtOH sessions, which increased by 2 hrs with each subsequent EtOH session until the amount of fluid/day was 10 hrs (last 2 EtOH sessions). EtOH intake in B6 mice was significantly greater than in D2 mice, with EtOH intake intermediate in the F2 cross of the 2 progenitor strains. Notably, EtOH intake in the D2 mice significantly decreased once total fluid/day was increased to 8-10 hrs. The short-term selected lines differed in EtOH intake during the 1st 2 EtOH sessions (STDRHI > STDRLO), but this initial difference disappeared with subsequent EtOH sessions. Blood EtOH concentration following the final EtOH session was significantly positively correlated with the EtOH dose consumed (r = 0.75, n = 36, p < 0.0001). Currently, we are using this model to examine EtOH intake in the genetically heterogeneous mice that will be the founding population for a selective breeding project (HS/Npt) to produce an animal model of high EtOH intake. The pattern of distribution of EtOH intake in genetically heterogeneous and B6D2F2 mice suggest that we will have no difficulty picking breeders for high EtOH intake. Supported by NIAAA INIA Consortium Grants AA13478 and AA13519 and the Dept. of Veterans Affairs.
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