Ethanol sensitivity in high drinking in the dark selectively bred mice

Abstract

Background: Mouse lines are being selectively bred in replicate for high blood ethanol concentrations (BECs) achieved after a short period of ethanol (EtOH) drinking early in the circadian dark phase. High Drinking in the Dark-1 (HDID-1) mice were in selected generation S18, and the replicate HDID-2 line in generation S11.

Methods: To determine other traits genetically correlated with high DID, we compared naïve animals from both lines with the unselected, segregating progenitor stock, HS/Npt. Differences between HDID-1 and HS would imply commonality of genetic influences on DID and these traits.

Results: HDID-1 mice showed less basal activity, greater EtOH stimulated activity, and greater sensitivity to EtOH-induced foot slips than HS. They showed lesser sensitivity to acute EtOH hypothermia and longer duration loss of righting reflex than HS. HDID-1 and control HS lines did not differ in sensitivity on 2 measures of intoxication, the balance beam and the accelerating rotarod. None of the acute response results could be explained by differences in EtOH metabolism. HDID-2 differed from HS on some, but not all, of the above responses.

Conclusions: These results show that some EtOH responses share common genetic control with reaching high BECs after DID, a finding consistent with other data regarding genetic contributions to EtOH responses.

Figure 1

Mean ± SE hind foot slips on the balance beam. Saline groups: N = 17, 15, and 16 for HS, HDID-1 and HDID-2, respectively. EtOH groups: N = 16 for each genotype.

Figure 2

Mean ± SE for scores in the parallel rod floor apparatus for three successive 5 minutes intervals after injection. Saline groups: N = 16 for all 3 genotypes. EtOH groups: N = 16, 15, and 14 for HS, HDID-1 and HDID-2, respectively. Panels A–C: Foot slips. Panels D–F: Locomotor activity (beam interruptions). Panels G–I: Foot slips corrected for activity (data from Panels A–C divided by data from panels D–F).

Figure 3

Mean ± SE latency to fall from the accelerating rotarod. Saline groups: N = 17, 16, and 17 for HS, HDID-1 and HDID-2, respectively. EtOH groups: N = 16, 17, and 17 for HS, HDID-1 and HDID-2, respectively. Panel A: Performance across the 10 acquisition trials on Day 1 for each genotype. Panel B: Average latency to fall across the 8 trials on Day 2 starting 30 minutes after saline or 2.0 g/kg EtOH.

Figure 3

Mean ± SE latency to fall from the accelerating rotarod. Saline groups: N = 17, 16, and 17 for HS, HDID-1 and HDID-2, respectively. EtOH groups: N = 16, 17, and 17 for HS, HDID-1 and HDID-2, respectively. Panel A: Performance across the 10 acquisition trials on Day 1 for each genotype. Panel B: Average latency to fall across the 8 trials on Day 2 starting 30 minutes after saline or 2.0 g/kg EtOH.

Figure 4

Mean ± SE body temperature (°C) before (Time 0) and after 3.0 g/kg EtOH. All mice (N = 32/genotype) were given EtOH. Panel A: Body temperature before and at 30 minute intervals after injection. Panel B: Total hypothermic response; approximate area under the hypothermia curves from Panel A.

Figure 4

Mean ± SE body temperature (°C) before (Time 0) and after 3.0 g/kg EtOH. All mice (N = 32/genotype) were given EtOH. Panel A: Body temperature before and at 30 minute intervals after injection. Panel B: Total hypothermic response; approximate area under the hypothermia curves from Panel A.