Intermittent availability of ethanol does not always lead to elevated drinking in mice

Abstract

Aims: Intermittent access (IA) to an alcohol (ethanol) solution can lead rats to higher ethanol intakes than continuous access, and a recent report showed increased drinking in C57BL/6J mice offered 20% ethanol vs. water 3X/week (Prior studies have offered ethanol during 24 h periods, either continuously or intermittently.).

Methods: We tested the high-preference C57BL/6J inbred mice: we also studied High Drinking in the Dark (HDID) mice, a line we have selectively bred to reach intoxicating blood ethanol levels after a short period of access to a single bottle of 20% ethanol.

Results: Neither HDID or C57BL/6J male mice offered ethanol every other day during only a 4-h access period showed greater daily intake than mice offered ethanol daily for 4 h. There was a small increase in drinking with 24 h IA in C57BL/6J mice. An experiment with HDID mice and their control heterogeneous stock stock modeled closely after a published study with C57BL/6J mice (Hwa, Chu, Levinson SA et al. Persistent escalation of alcohol drinking in C57BL/6J mice with intermittent access to 20% ethanol. Alcohol Clin Exp Res 2011;35:1938-1947) showed no significant elevation with 24 h IA exposure in either sex of any genotype. Finally, a near replication of the Hwa et al. study showed modestly greater intake in C57BL/6J mice, confirming the efficacy of 24 h IA.

Conclusion: We conclude that 4 h of IA is likely insufficient to elevate drinking in mice. The lack of effect in HDID mice and their controls further suggests that not all genotypes respond to intermittency.

Fig. 1.

Drinking in HDID-1 male mice with intermittent (closed symbols) or continuous (open symbols) access to a single bottle of 20% ethanol 4 h/day. Daily intakes during the first week are shown in the left panel. Access was for only 2 h on the first 2 days of Week 1. Average drinking for MWF in Weeks 2–5 is shown in the right panels. Means ± SE are shown.

Fig. 2.

Drinking in C57BL/6J male mice with intermittent (closed symbols) or continuous (open symbols) access to a single bottle of 20% ethanol 4 h/day. See caption to Fig. 1.

Fig. 3.

Drinking in C57BL/6J male mice with intermittent (closed symbols) or continuous (open symbols) access to a 20% ethanol 24 h/day. Daily intakes during Week 1 are shown in the left panel. Average drinking for MWF in Weeks 2 and 3 is shown in the right panels. Means ± SE are shown.

Fig. 4.

Drinking in HDID-1 (a) HDID-2 (b) and heterogeneous stock (HS) (c) female mice with intermittent (closed symbols) or continuous (open symbols) access to ethanol 24 h/day. Daily intakes for MWF during the first week and on M of Week 2 are shown in the left panels. Weekly drinking averaged across MWF in Weeks 2–4 is shown in the right panels. Means ± SE are shown.

Fig. 5.

Drinking in HDID-1 (a) HDID-2 (b) and HS (c) male mice with intermittent (closed symbols) or continuous (open symbols) access to ethanol 24 h/day. See caption to Fig. 4.

Fig. 6.

Average drinking on MWF each week in C57BL/6J female (a) and male (b) mice with intermittent (closed symbols) or continuous (open symbols) access to ethanol 24 h/day. EtOH concentration remained at 20% after M of Week 2. Means ± SE are shown.