Sensitivity and tolerance to ethanol in mouse lines selected for ethanol-induced hypothermia

Kaitlin E. Browman, Nathan R. Rustay, Natasha Nikolaidis, Larry Crawshaw, John Jr Crabbe

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Within-family selective breeding techniques have been used to create two lines of mice to be insensitive (HOT) and two lines to be sensitive (COLD) to the hypothermic effects of an acute 3.0-g/kg ethanol (EtOH) injection. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. The breeding program is currently in selected Generation 52, and the HOT and COLD mice differ by about 10°C (average of both replicates) in their selected hypothermic response. Starting with selection Generation 20, separate lines of mice were inbred from the HOT-2 and COLD-2 selected lines, while selection continued for the original two replicate lines of HOT and COLD mice. To assess whether different dose treatments would produce differential tolerance development in the HOT and COLD selected lines, we administered different dose regimens across 5 days to HOT and COLD mice. The COLD mice developed tolerance while the HOT mice did not, regardless of total EtOH administered. In a separate study, we administered EtOH (3.0 g/kg) to mice for 3 days to assess a shorter tolerance paradigm. We also present here responses to the selection dose of 3.0-g/kg EtOH in the inbred HOT (IHOT-2) and COLD (ICOLD-2) mice tested after 41 generations of brother-sister mating. In addition, we report recent attempts to find doses of EtOH that would produce an equivalent initial hypothermic response in each of the six lines (HOT-1, COLD-1, HOT-2, COLD-2, ICOLD-2, and IHOT-2). When doses were selected to produce similar initial hypothermic sensitivity, tolerance was tested by giving three daily doses and examining the attenuation of the hypothermic response on the third day. All three COLD lines developed significant tolerance, while the HOT lines did not. The HOT and COLD mice provide a genetic model to study mechanisms mediating acute EtOH-induced hypothermia as well as tolerance development.

Original languageEnglish (US)
Pages (from-to)821-829
Number of pages9
JournalPharmacology Biochemistry and Behavior
Volume67
Issue number4
DOIs
StatePublished - 2000

Fingerprint

Hypothermia
Induced Hypothermia
Ethanol
Genetic Models
Breeding

Keywords

  • COLD mice
  • Ethanol
  • HOT mice
  • Hypothermia
  • Inbred strains
  • Selected lines
  • Tolerance

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Sensitivity and tolerance to ethanol in mouse lines selected for ethanol-induced hypothermia. / Browman, Kaitlin E.; Rustay, Nathan R.; Nikolaidis, Natasha; Crawshaw, Larry; Crabbe, John Jr.

In: Pharmacology Biochemistry and Behavior, Vol. 67, No. 4, 2000, p. 821-829.

Research output: Contribution to journalArticle

Browman, Kaitlin E. ; Rustay, Nathan R. ; Nikolaidis, Natasha ; Crawshaw, Larry ; Crabbe, John Jr. / Sensitivity and tolerance to ethanol in mouse lines selected for ethanol-induced hypothermia. In: Pharmacology Biochemistry and Behavior. 2000 ; Vol. 67, No. 4. pp. 821-829.
@article{9ab0493d37ff4f99ad2cad4bd94f2bff,
title = "Sensitivity and tolerance to ethanol in mouse lines selected for ethanol-induced hypothermia",
abstract = "Within-family selective breeding techniques have been used to create two lines of mice to be insensitive (HOT) and two lines to be sensitive (COLD) to the hypothermic effects of an acute 3.0-g/kg ethanol (EtOH) injection. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. The breeding program is currently in selected Generation 52, and the HOT and COLD mice differ by about 10°C (average of both replicates) in their selected hypothermic response. Starting with selection Generation 20, separate lines of mice were inbred from the HOT-2 and COLD-2 selected lines, while selection continued for the original two replicate lines of HOT and COLD mice. To assess whether different dose treatments would produce differential tolerance development in the HOT and COLD selected lines, we administered different dose regimens across 5 days to HOT and COLD mice. The COLD mice developed tolerance while the HOT mice did not, regardless of total EtOH administered. In a separate study, we administered EtOH (3.0 g/kg) to mice for 3 days to assess a shorter tolerance paradigm. We also present here responses to the selection dose of 3.0-g/kg EtOH in the inbred HOT (IHOT-2) and COLD (ICOLD-2) mice tested after 41 generations of brother-sister mating. In addition, we report recent attempts to find doses of EtOH that would produce an equivalent initial hypothermic response in each of the six lines (HOT-1, COLD-1, HOT-2, COLD-2, ICOLD-2, and IHOT-2). When doses were selected to produce similar initial hypothermic sensitivity, tolerance was tested by giving three daily doses and examining the attenuation of the hypothermic response on the third day. All three COLD lines developed significant tolerance, while the HOT lines did not. The HOT and COLD mice provide a genetic model to study mechanisms mediating acute EtOH-induced hypothermia as well as tolerance development.",
keywords = "COLD mice, Ethanol, HOT mice, Hypothermia, Inbred strains, Selected lines, Tolerance",
author = "Browman, {Kaitlin E.} and Rustay, {Nathan R.} and Natasha Nikolaidis and Larry Crawshaw and Crabbe, {John Jr}",
year = "2000",
doi = "10.1016/S0091-3057(00)00427-5",
language = "English (US)",
volume = "67",
pages = "821--829",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Sensitivity and tolerance to ethanol in mouse lines selected for ethanol-induced hypothermia

AU - Browman, Kaitlin E.

AU - Rustay, Nathan R.

AU - Nikolaidis, Natasha

AU - Crawshaw, Larry

AU - Crabbe, John Jr

PY - 2000

Y1 - 2000

N2 - Within-family selective breeding techniques have been used to create two lines of mice to be insensitive (HOT) and two lines to be sensitive (COLD) to the hypothermic effects of an acute 3.0-g/kg ethanol (EtOH) injection. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. The breeding program is currently in selected Generation 52, and the HOT and COLD mice differ by about 10°C (average of both replicates) in their selected hypothermic response. Starting with selection Generation 20, separate lines of mice were inbred from the HOT-2 and COLD-2 selected lines, while selection continued for the original two replicate lines of HOT and COLD mice. To assess whether different dose treatments would produce differential tolerance development in the HOT and COLD selected lines, we administered different dose regimens across 5 days to HOT and COLD mice. The COLD mice developed tolerance while the HOT mice did not, regardless of total EtOH administered. In a separate study, we administered EtOH (3.0 g/kg) to mice for 3 days to assess a shorter tolerance paradigm. We also present here responses to the selection dose of 3.0-g/kg EtOH in the inbred HOT (IHOT-2) and COLD (ICOLD-2) mice tested after 41 generations of brother-sister mating. In addition, we report recent attempts to find doses of EtOH that would produce an equivalent initial hypothermic response in each of the six lines (HOT-1, COLD-1, HOT-2, COLD-2, ICOLD-2, and IHOT-2). When doses were selected to produce similar initial hypothermic sensitivity, tolerance was tested by giving three daily doses and examining the attenuation of the hypothermic response on the third day. All three COLD lines developed significant tolerance, while the HOT lines did not. The HOT and COLD mice provide a genetic model to study mechanisms mediating acute EtOH-induced hypothermia as well as tolerance development.

AB - Within-family selective breeding techniques have been used to create two lines of mice to be insensitive (HOT) and two lines to be sensitive (COLD) to the hypothermic effects of an acute 3.0-g/kg ethanol (EtOH) injection. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. The breeding program is currently in selected Generation 52, and the HOT and COLD mice differ by about 10°C (average of both replicates) in their selected hypothermic response. Starting with selection Generation 20, separate lines of mice were inbred from the HOT-2 and COLD-2 selected lines, while selection continued for the original two replicate lines of HOT and COLD mice. To assess whether different dose treatments would produce differential tolerance development in the HOT and COLD selected lines, we administered different dose regimens across 5 days to HOT and COLD mice. The COLD mice developed tolerance while the HOT mice did not, regardless of total EtOH administered. In a separate study, we administered EtOH (3.0 g/kg) to mice for 3 days to assess a shorter tolerance paradigm. We also present here responses to the selection dose of 3.0-g/kg EtOH in the inbred HOT (IHOT-2) and COLD (ICOLD-2) mice tested after 41 generations of brother-sister mating. In addition, we report recent attempts to find doses of EtOH that would produce an equivalent initial hypothermic response in each of the six lines (HOT-1, COLD-1, HOT-2, COLD-2, ICOLD-2, and IHOT-2). When doses were selected to produce similar initial hypothermic sensitivity, tolerance was tested by giving three daily doses and examining the attenuation of the hypothermic response on the third day. All three COLD lines developed significant tolerance, while the HOT lines did not. The HOT and COLD mice provide a genetic model to study mechanisms mediating acute EtOH-induced hypothermia as well as tolerance development.

KW - COLD mice

KW - Ethanol

KW - HOT mice

KW - Hypothermia

KW - Inbred strains

KW - Selected lines

KW - Tolerance

UR - http://www.scopus.com/inward/record.url?scp=0034488603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034488603&partnerID=8YFLogxK

U2 - 10.1016/S0091-3057(00)00427-5

DO - 10.1016/S0091-3057(00)00427-5

M3 - Article

C2 - 11166073

AN - SCOPUS:0034488603

VL - 67

SP - 821

EP - 829

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

IS - 4

ER -