Mouse lines selected for genetic differences in diazepam sensitivity

E. J. Gallaher, L. E. Hollister, S. E. Gionet, John Jr Crabbe

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Selective breeding techniques were used to alter allelic frequencies responsible for diazepam sensitivity and resistance. We used the rotarod test to determine the duration of diazepam-induced neurologic deficit in genetically heterogeneous mice. Males were more sensitive than females in the initial population. We then selectively bred for diazepam resistance and sensitivity. A significant difference between the lines was apparent in both sexes after two generations, and divergence has continued over seven generations. Brain benzodiazepine assays indicated that absorption and distribution of diazepam do not differ in the two lines. Differences in brain benzodiazepine concentrations at recovery from ataxia indicated that the two lines differ in central nervous system sensitivity. We found diazepam-induced rotarod impairment to be blocked in a dose-dependent manner by the specific benzodiazepine antagonist Ro 15-1788, indicating that this effect is mediated through BZ receptors. A dose-response curve obtained from generations 6 and 7 indicates a 9- to 14-fold difference in dose required to obtain similar effects in the two lines. These mice are expected to be useful experimental subjects in studies of benzodiazepine mechanisms.

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalPsychopharmacology
Volume93
Issue number1
DOIs
StatePublished - Sep 1987

Fingerprint

Diazepam
Benzodiazepines
Rotarod Performance Test
Flumazenil
Brain
Ataxia
Neurologic Manifestations
Central Nervous System
Population

Keywords

  • Behavior genetics
  • Benzodiazepines
  • Diazepam
  • DS and DR lines
  • Pharmacogenetics
  • Psychopharmacology
  • Rotarod
  • Selective breeding

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mouse lines selected for genetic differences in diazepam sensitivity. / Gallaher, E. J.; Hollister, L. E.; Gionet, S. E.; Crabbe, John Jr.

In: Psychopharmacology, Vol. 93, No. 1, 09.1987, p. 25-30.

Research output: Contribution to journalArticle

Gallaher, E. J. ; Hollister, L. E. ; Gionet, S. E. ; Crabbe, John Jr. / Mouse lines selected for genetic differences in diazepam sensitivity. In: Psychopharmacology. 1987 ; Vol. 93, No. 1. pp. 25-30.
@article{69891555e1f44bbda15f5cf2ff062e94,
title = "Mouse lines selected for genetic differences in diazepam sensitivity",
abstract = "Selective breeding techniques were used to alter allelic frequencies responsible for diazepam sensitivity and resistance. We used the rotarod test to determine the duration of diazepam-induced neurologic deficit in genetically heterogeneous mice. Males were more sensitive than females in the initial population. We then selectively bred for diazepam resistance and sensitivity. A significant difference between the lines was apparent in both sexes after two generations, and divergence has continued over seven generations. Brain benzodiazepine assays indicated that absorption and distribution of diazepam do not differ in the two lines. Differences in brain benzodiazepine concentrations at recovery from ataxia indicated that the two lines differ in central nervous system sensitivity. We found diazepam-induced rotarod impairment to be blocked in a dose-dependent manner by the specific benzodiazepine antagonist Ro 15-1788, indicating that this effect is mediated through BZ receptors. A dose-response curve obtained from generations 6 and 7 indicates a 9- to 14-fold difference in dose required to obtain similar effects in the two lines. These mice are expected to be useful experimental subjects in studies of benzodiazepine mechanisms.",
keywords = "Behavior genetics, Benzodiazepines, Diazepam, DS and DR lines, Pharmacogenetics, Psychopharmacology, Rotarod, Selective breeding",
author = "Gallaher, {E. J.} and Hollister, {L. E.} and Gionet, {S. E.} and Crabbe, {John Jr}",
year = "1987",
month = "9",
doi = "10.1007/BF02439582",
language = "English (US)",
volume = "93",
pages = "25--30",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Mouse lines selected for genetic differences in diazepam sensitivity

AU - Gallaher, E. J.

AU - Hollister, L. E.

AU - Gionet, S. E.

AU - Crabbe, John Jr

PY - 1987/9

Y1 - 1987/9

N2 - Selective breeding techniques were used to alter allelic frequencies responsible for diazepam sensitivity and resistance. We used the rotarod test to determine the duration of diazepam-induced neurologic deficit in genetically heterogeneous mice. Males were more sensitive than females in the initial population. We then selectively bred for diazepam resistance and sensitivity. A significant difference between the lines was apparent in both sexes after two generations, and divergence has continued over seven generations. Brain benzodiazepine assays indicated that absorption and distribution of diazepam do not differ in the two lines. Differences in brain benzodiazepine concentrations at recovery from ataxia indicated that the two lines differ in central nervous system sensitivity. We found diazepam-induced rotarod impairment to be blocked in a dose-dependent manner by the specific benzodiazepine antagonist Ro 15-1788, indicating that this effect is mediated through BZ receptors. A dose-response curve obtained from generations 6 and 7 indicates a 9- to 14-fold difference in dose required to obtain similar effects in the two lines. These mice are expected to be useful experimental subjects in studies of benzodiazepine mechanisms.

AB - Selective breeding techniques were used to alter allelic frequencies responsible for diazepam sensitivity and resistance. We used the rotarod test to determine the duration of diazepam-induced neurologic deficit in genetically heterogeneous mice. Males were more sensitive than females in the initial population. We then selectively bred for diazepam resistance and sensitivity. A significant difference between the lines was apparent in both sexes after two generations, and divergence has continued over seven generations. Brain benzodiazepine assays indicated that absorption and distribution of diazepam do not differ in the two lines. Differences in brain benzodiazepine concentrations at recovery from ataxia indicated that the two lines differ in central nervous system sensitivity. We found diazepam-induced rotarod impairment to be blocked in a dose-dependent manner by the specific benzodiazepine antagonist Ro 15-1788, indicating that this effect is mediated through BZ receptors. A dose-response curve obtained from generations 6 and 7 indicates a 9- to 14-fold difference in dose required to obtain similar effects in the two lines. These mice are expected to be useful experimental subjects in studies of benzodiazepine mechanisms.

KW - Behavior genetics

KW - Benzodiazepines

KW - Diazepam

KW - DS and DR lines

KW - Pharmacogenetics

KW - Psychopharmacology

KW - Rotarod

KW - Selective breeding

UR - http://www.scopus.com/inward/record.url?scp=0023620149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023620149&partnerID=8YFLogxK

U2 - 10.1007/BF02439582

DO - 10.1007/BF02439582

M3 - Article

C2 - 2819924

AN - SCOPUS:0023620149

VL - 93

SP - 25

EP - 30

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 1

ER -