Environmental variables differentially affect ethanol-stimulated activity in selectively bred mouse lines

Abstract

Low doses of ethanol (EtOH) stimulate activity in an open field in many strains of laboratory mice. We are selectively breeding two lines of mice to exhibit a large (FAST) response on this test, and two other lines to exhibit a small (SLOW) response (Crabbe et al. 1987). The lines initially diverged in response to EtOH, but despite continued selection pressure, the difference between each pair of FAST and SLOW lines has not increased over generations as much as expected. Our practice has been to test animals on the 1st day after saline injection, and repeat the test after EtOH injection 24 h later. Lister (1987) recently demonstrated that the order in which an animal was exposed to EtOH and saline influenced the magnitude of the response to EtOH, with animals tested initially after EtOH having greater stimulation. Middaugh et al. (1987) recently demonstrated that the magnitude of EtOH stimulation was greater under conditions of relatively bright light than under dim light. Using non-selected Swiss mice, the current experiments essentially confirmed Lister's findings. Using FAST and SLOW mice, the predictions of both groups were tested. Both hypotheses were confirmed. Additionally, these experiments demonstrated that the magnitude of the difference between FAST and SLOW mice was greater under bright light than under dim light. The line difference was also greater when tested in the EtOH-Saline order. In experiments with Swiss mice, the possible role of peritoneal irritation in the EtOH effect was eliminated, and the optimal dose and time for demonstrating the effect was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of novelty, isolation, light and ethanol on the social behavior of mice

“…In the present study, activity was lower under the high than in the low illumination level and was also lower when the test environment was familiar than when it was unfamiliar. These data parallel those of Nagy and Glaser (1970), of Middaugh et al (1987) and of Crabbe et al (1988).…”

Attenuation of the Stimulant Response to Ethanol is Associated with Enhanced Ataxia for a GABAA, but not a GABAB, Receptor Agonist

“…Details specific to the selection process have been published (Crabbe et al, 1987, 1988; Phillips et al, 1991, 2002; Shen et al, 1995). The most recent test of the ethanol dose-response function in these mice (~20 generations since selection was relaxed) showed that FAST mice were significantly different from SLOW mice in their locomotor response to multiple ethanol doses (i.e., 1.5, 2, 2.5, and 3 g/kg).…”

“…Subjects were not habituated to the activity monitor or to injections prior to locomotor testing, consistent with the selection procedure (Crabbe et al, 1988; Phillips et al, 1991), as well as previous experiments using GABA mimetic compounds in FAST mice (Palmer et al, 2002a,b; Phillips et al, 1992; Shen et al, 1998). Mice were weighed, injected with the pretreatment drug (saline, NO-711, muscimol, or baclofen), and placed individually into holding cages.…”

GABAB receptor stimulation accentuates the locomotor effects of morphine in mice bred for extreme sensitivity to the stimulant effects of ethanol

“…The two activity tests were performed 24-h apart. Subsequent to selection generation 37 (S 37 ), breeding of the FAST and SLOW lines has been performed under relaxed selection conditions, with mice chosen randomly and bred within line (Crabbe et al, 1987(Crabbe et al, , 1988Phillips et al, 1991Phillips et al, , 2002Shen et al, 1995b) Experimentally naïve male FAST-1 and FAST-2 mice from the S 37 G 72-76 generations (S xx refers to the number of selection generations; G yy refers to the total number of elapsed generations since the beginning of selection) were used for the current studies. Only male mice were used due to their greater availability and because previous studies using baclofen in FAST mice did not find sex-specific effects (Boehm et al, 2002;Shen et al, 1998).…”