05 compared with 15 min, one-sample t -test). … Discussion We investigated whether B6129 hybrid mice show significant differences in ethanol-related phenotypes when compared with their B6 inbred counterparts. We observed the greatest behavioral differences in the continuous access, two-bottle choice test, where hybrid mice consumed significantly less ethanol than inbred mice. In Erlotinib supplier contrast, in the limited access procedure, differences were less pronounced. Indeed, one hybrid line, B6129S4, consumed more than its corresponding inbred line B6J. B6J inbred and hybrid lines showed similar ethanol clearance. In contrast, the comparison of the B6NT mice with B6129S6 mice showed that the hybrid has slower
ethanol clearance but only at Inhibitors,research,lifescience,medical later time points, 2–3 h following ethanol administration. There was no difference between inbred and hybrid lines
in the duration of the Inhibitors,research,lifescience,medical LORR. Further, all strains developed a modest CPP for ethanol, with slight differences in magnitude. These results indicate that B6 mice and the related three hybrid lines examined here perform similarly on all behavioral Inhibitors,research,lifescience,medical tests except those involving ethanol consumption. The continuous access two-bottle choice procedure is commonly used to study ethanol self-administration in mice. As expected based on prior studies of ethanol intake in B6 and 129 mice (Belknap et al. 1993; Bachmanov et al. 1996; Yoneyama et al. 2008), we found that B6 mice increased their consumption of ethanol at concentrations that produced a reduction of ethanol consumption and preference in hybrid mice. Hybrid lines showed maximal ethanol consumption with 10% ethanol, while inbred lines peaked at 14%. All lines reduced their ethanol consumption and preference with 20% ethanol, suggesting aversion Inhibitors,research,lifescience,medical for this concentration. These results indicate that inbred B6 mice are better suited than B6 × 129 hybrid mice for studying high levels of ethanol consumption in a continuous access procedure. However, hybrid mice may be better
suited for detecting the ability of gene selleck chemical SB203580 disruption to increase drinking in this procedure. Although Inhibitors,research,lifescience,medical the continuous access paradigm can be used to screen for differences in low-to-moderate ethanol consumption, rodents may not consume enough ethanol in this procedure to become intoxicated (Spanagel 2000). GSK-3 To study higher levels of ethanol consumption, investigators have used limited access paradigms providing ethanol in the dark when rodents are more active (Rhodes et al. 2005, 2007; Neasta et al. 2010). In variations of the procedure, mice can consume enough ethanol to reach BECs greater than 80 mg/dL, the level of legal intoxication in many states of the United States (NIAAA 2004). Interestingly, the hybrid strains, which showed low levels of consumption and preference in the continuous access two-bottle choice test at high ethanol concentrations, consumed high levels of 20% ethanol more similar to, or in the case of the B6129S4 mice, slightly greater than their B6 counterparts.