Sleep time following anesthesia in mouse lines selected for resistance or susceptibility to fescue toxicosis K. A. Arthur, L. A. Kuehn, and W. D. Hohenboken 1 Animal and Poultry Sciences Department, Virginia Polytechnic Institute and State University, Blacksburg 24061-0306 ABSTRACT: In previous work, a mouse line selected for resistance (R) to fescue toxicosis had higher activi- ties of two hepatic Phase II detoxification enzymes than a mouse line selected for fescue toxicosis susceptibility (S). The primary objective of the present study was to determine whether those same lines also differed in hepatic Phase I enzyme activity, estimated from sleep time (ST) following sodium pentobarbital anesthesia. Additional objectives were to determine whether ST differences between lines were modulated by endo- phyte-infected fescue in the diet (with or without an enzyme inducer) and whether ST of individual mice was correlated with the effect of a toxin-containing diet on the postweaning growth of those mice. In Exp. I, 24 males from each line were randomly assigned to each of five diets: control (commercial rodent food meal); E+ (50% endophyte-infected fescue seed, 50% control); E+P (the E+ diet supplemented with 1,000 ppm phenobarbi- tal); E- (50% endophyte-free fescue seed, 50% control); and E-P (the E- diet supplemented with 1,000 ppm phenobarbital). After 4 wk on these diets, ST was mea- sured on all the mice. A second ST was recorded on Key Words: Anesthesia, Festuca, Mice, Resistance, Susceptibility, Toxicity 2003 American Society of Animal Science. All rights reserved. J. Anim. Sci. 2003. 81:2562–2567 Introduction Fescue toxicosis results in annual production losses to U.S. livestock and horse industries of more than $1 billion (Hoveland, 1993; Cross, 1997). Management practices designed to alleviate its impact have not been universally effective. Selection within (Lipsey et al., 1992) or between cattle breeds (Nutting et al., 1992) for response to endophyte-infected (E+) fescue is a po- tential genetic solution. Before effective strategies can 1 Correspondence—phone: 540-552-2817; fax: 540-231-3010; E- mail; whohenbo@vt.edu. Received January 27, 2003. Accepted June 2, 2003. 2562 each mouse by randomly sampling one-fourth of the population after 1, 2, 3, or 4 wk on a pelleted rodent food diet. Regardless of diet, R mice had shorter first and second ST than S mice (P < 0.01), suggesting higher hepatic Phase I microsomal enzyme activity. Mice on both phenobarbital-supplemented diets had shorter first ST than mice whose diets did not include that microsomal enzyme inducer (P < 0.01). In Exp. II, ST was measured on male and female R and S mice (n = 280) after they had been fed the E- diet for 2 wk, then the E+ diet for 2 wk, and then a pelleted rodent food diet for 2 wk. Growth response to the E+ diet was the percentage of reduction in gain on the E+ diet compared to gain on the E- diet the previous 2 wk. As in Exp. I, S mice slept longer than R mice (P < 0.01). The residual correlation between ST and gain reduction associated with the E+ diet equaled 0.04. Thus, an animal’s appar- ent Phase I enzyme activity did not predict its growth rate depression on the toxin-containing diet. Based on these and previous studies, divergent selection for toxi- cosis response in mice was successful partially by caus- ing divergence in activities of hepatic Phase I and II detoxification enzymes. be designed, however, biology of host resistance to the toxins must be examined. Hohenboken and Blodgett (1997) selected mouse lines for resistance (R) or susceptibility (S) to the effect on postweaning growth of E+ fescue seed in the diet. After eight generations of selection, the lines differed in the impact of an E+ diet on growth, and R mice had higher hepatic Phase II enzyme activities than S mice (Hohenboken and Blodgett, 1997). Reproduction in the S line was more severely depressed by an E+ diet than was reproduction in the R line (Wagner et al., 2000), and R mice had higher resistance than S mice to the mycotoxin, sporidesmin (Hohenboken et al., 2000). Our primary objective was to determine whether the R and S lines differ in hepatic Phase I detoxification function as assessed by sleep time following sodium pentobarbital anesthesia (ST). In Exp. I, we sought to