Chronic ethanol consumption produces genotype-dependent tolerance to ethanol in LS/Ibg and SS/Ibg mice

V. G. Erwin, R. A. Radcliffe, Byron Jones

Research output: Contribution to journalArticle

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Abstract

It is well known that chronic ethanol administration produces tolerance to the sedative-hypnotic and hypothermic effects as well as low-dose locomotor inhibitory effects of ethanol. We report herein characterization of a convenient method of producing genotype-dependent functional tolerance to ethanol-induced locomotor inhibition. Mice, LS/Ibg (LS) and SS/Ibg (SS), which differ markedly in acute effects of ethanol on locomotor activity, hypothermia, and hypnotic sensitivity, were required to consume solutions of ethanol in water as the sole source of liquid. Mice were provided lab chow ad lib. and the following regimen of ethanol in water, v/v: 10% for 4 days, 15% for 7 days, 20% for 7 days, followed by 15% for periods longer than 2 weeks. Control animals received water only or were pair-fed sucrose (isocaloric with ethanol) solutions plus lab chow; both control and ethanol-consuming (15 g ethanol/kg/24 h) mice maintained similar body weights for up to 4 weeks. Blood ethanol concentrations from 10-200 mg% were obtained during a 12 L:12 D cycle. At 6 h following withdrawal, LS and SS mice showed differential dose-dependent tolerance to locomotor inhibitory effects of ethanol. However, low-dose locomotor activation was unaltered in either line of mice, and results indicate that an apparent sensitization in SS mice is secondary to development of tolerance to locomotor inhibition. Maximum tolerance to locomotor inhibition was observed after 2 weeks of chronic ethanol consumption, with responses returning to control values within 1-2 weeks after withdrawal. Rates of acquisition of tolerance were similar in LS and SS mice. LS but not SS mice developed tolerance to ethanol-induced hypothermia, but neither line acquired tolerance to the hypnotic effects of ethanol. While LS mice acquired some metabolic tolerance, tolerance to locomotor inhibition or hypothermia was not mediated by alterations in ethanol elimination rates indicating marked neuroadaptation, that is, changes in CNS sensitivity. Only slight hypothermia and zero scores for handling-induced seizures were observed after withdrawal from 2-4 weeks of chronic ethanol intake. The results indicate that different genotype-dependent mechanisms may mediate or modulate hypnotic effects and activating or inhibitory effects of subhypnotic doses of ethanol and that these processes respond differentially to chronic ethanol intake. It is proposed that this ethanol intake model will be valuable in examining neurochemical processes hypothesized to mediate neuroadaptation to locomotor inhibitory effects of ethanol.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalPharmacology, Biochemistry and Behavior
Volume41
Issue number2
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

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Ethanol
Genotype
Hypothermia
Hypnotics and Sedatives
Water
Induced Hypothermia
Locomotion
Sucrose
Animals
Seizures
Blood

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Chronic ethanol consumption produces genotype-dependent tolerance to ethanol in LS/Ibg and SS/Ibg mice. / Erwin, V. G.; Radcliffe, R. A.; Jones, Byron.

In: Pharmacology, Biochemistry and Behavior, Vol. 41, No. 2, 01.01.1992, p. 275-281.

Research output: Contribution to journalArticle

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abstract = "It is well known that chronic ethanol administration produces tolerance to the sedative-hypnotic and hypothermic effects as well as low-dose locomotor inhibitory effects of ethanol. We report herein characterization of a convenient method of producing genotype-dependent functional tolerance to ethanol-induced locomotor inhibition. Mice, LS/Ibg (LS) and SS/Ibg (SS), which differ markedly in acute effects of ethanol on locomotor activity, hypothermia, and hypnotic sensitivity, were required to consume solutions of ethanol in water as the sole source of liquid. Mice were provided lab chow ad lib. and the following regimen of ethanol in water, v/v: 10{\%} for 4 days, 15{\%} for 7 days, 20{\%} for 7 days, followed by 15{\%} for periods longer than 2 weeks. Control animals received water only or were pair-fed sucrose (isocaloric with ethanol) solutions plus lab chow; both control and ethanol-consuming (15 g ethanol/kg/24 h) mice maintained similar body weights for up to 4 weeks. Blood ethanol concentrations from 10-200 mg{\%} were obtained during a 12 L:12 D cycle. At 6 h following withdrawal, LS and SS mice showed differential dose-dependent tolerance to locomotor inhibitory effects of ethanol. However, low-dose locomotor activation was unaltered in either line of mice, and results indicate that an apparent sensitization in SS mice is secondary to development of tolerance to locomotor inhibition. Maximum tolerance to locomotor inhibition was observed after 2 weeks of chronic ethanol consumption, with responses returning to control values within 1-2 weeks after withdrawal. Rates of acquisition of tolerance were similar in LS and SS mice. LS but not SS mice developed tolerance to ethanol-induced hypothermia, but neither line acquired tolerance to the hypnotic effects of ethanol. While LS mice acquired some metabolic tolerance, tolerance to locomotor inhibition or hypothermia was not mediated by alterations in ethanol elimination rates indicating marked neuroadaptation, that is, changes in CNS sensitivity. Only slight hypothermia and zero scores for handling-induced seizures were observed after withdrawal from 2-4 weeks of chronic ethanol intake. The results indicate that different genotype-dependent mechanisms may mediate or modulate hypnotic effects and activating or inhibitory effects of subhypnotic doses of ethanol and that these processes respond differentially to chronic ethanol intake. It is proposed that this ethanol intake model will be valuable in examining neurochemical processes hypothesized to mediate neuroadaptation to locomotor inhibitory effects of ethanol.",
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