Effect of forward and reverse selection for ethanol-induced locomotor response on other measures of ethanol sensitivity

Abraham A. Palmer, Tamara Phillips

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Ethanol sensitivity may be a predictor of genetic predisposition to ethanol abuse. To examine ethanol sensitivity in rodents, two lines of mice were bred in replicate for high (FAST-1 and -2) and low (SLOW-1 and -2) locomotor stimulant responses to ethanol. After large differences between the lines developed and further response to selection seemed to have arrested, reverse selection was initiated by breeding the slowest FAST mice with each other and the fastest SLOW mice with each other. The reverse-selected lines, named r-FAST and r-SLOW, were virtually equally sensitive to the stimulant effects of the selection dose of ethanol after 16 generations of reverse selection. Methods: These experiments used this unique genetic model to examine two responses, putatively genetically correlated with sensitivity to ethanol stimulation: handling-induced convulsions during chronic ethanol withdrawal, and ethanol-induced hypothermia. Ethanol clearance, for which a small difference was previously found between the FAST and SLOW lines, was also examined. Results: Handling-induced convulsions during chronic ethanol withdrawal were significantly greater in both FAST lines compared with both SLOW lines. Reverse selection eliminated the difference between the replicate 1 lines but did not alter the difference between the replicate 2 lines. Ethanol-induced hypothermia was greater in both SLOW lines compared with the FAST lines. This difference was significantly reduced by reverse selection in r-SLOW mice only. Ethanol clearance rates were similar among all lines and replicates. Conclusions: These data demonstrate the usefulness of reverse-selected lines for examining putatively genetically correlated traits. Changes in the correlated traits demonstrated the existence of persistent trait-relevant genetic heterogeneity and some genetic overlap between the correlated traits and the selection trait. Absence of a change after reverse selection suggests that trait-relevant genetic heterogeneity was eliminated by forward selection or, alternatively, that the trait was not influenced by genes associated with successful reverse selection.

Original languageEnglish (US)
Pages (from-to)1322-1329
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume26
Issue number9
DOIs
StatePublished - Sep 2002

Fingerprint

Ethanol
Hypothermia
Induced Hypothermia
Genetic Heterogeneity
Seizures
Genetic Models
Genetic Predisposition to Disease
Breeding
Rodentia
Genes

Keywords

  • Chronic ethanol withdrawal
  • Ethanol metabolism
  • Hypothermia
  • Locomotor stimulation
  • Reverse Selection

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

@article{e106ca4afdd64c7c8c4695a1e3e0c39b,
title = "Effect of forward and reverse selection for ethanol-induced locomotor response on other measures of ethanol sensitivity",
abstract = "Background: Ethanol sensitivity may be a predictor of genetic predisposition to ethanol abuse. To examine ethanol sensitivity in rodents, two lines of mice were bred in replicate for high (FAST-1 and -2) and low (SLOW-1 and -2) locomotor stimulant responses to ethanol. After large differences between the lines developed and further response to selection seemed to have arrested, reverse selection was initiated by breeding the slowest FAST mice with each other and the fastest SLOW mice with each other. The reverse-selected lines, named r-FAST and r-SLOW, were virtually equally sensitive to the stimulant effects of the selection dose of ethanol after 16 generations of reverse selection. Methods: These experiments used this unique genetic model to examine two responses, putatively genetically correlated with sensitivity to ethanol stimulation: handling-induced convulsions during chronic ethanol withdrawal, and ethanol-induced hypothermia. Ethanol clearance, for which a small difference was previously found between the FAST and SLOW lines, was also examined. Results: Handling-induced convulsions during chronic ethanol withdrawal were significantly greater in both FAST lines compared with both SLOW lines. Reverse selection eliminated the difference between the replicate 1 lines but did not alter the difference between the replicate 2 lines. Ethanol-induced hypothermia was greater in both SLOW lines compared with the FAST lines. This difference was significantly reduced by reverse selection in r-SLOW mice only. Ethanol clearance rates were similar among all lines and replicates. Conclusions: These data demonstrate the usefulness of reverse-selected lines for examining putatively genetically correlated traits. Changes in the correlated traits demonstrated the existence of persistent trait-relevant genetic heterogeneity and some genetic overlap between the correlated traits and the selection trait. Absence of a change after reverse selection suggests that trait-relevant genetic heterogeneity was eliminated by forward selection or, alternatively, that the trait was not influenced by genes associated with successful reverse selection.",
keywords = "Chronic ethanol withdrawal, Ethanol metabolism, Hypothermia, Locomotor stimulation, Reverse Selection",
author = "Palmer, {Abraham A.} and Tamara Phillips",
year = "2002",
month = "9",
doi = "10.1097/00000374-200209000-00003",
language = "English (US)",
volume = "26",
pages = "1322--1329",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Effect of forward and reverse selection for ethanol-induced locomotor response on other measures of ethanol sensitivity

AU - Palmer, Abraham A.

AU - Phillips, Tamara

PY - 2002/9

Y1 - 2002/9

N2 - Background: Ethanol sensitivity may be a predictor of genetic predisposition to ethanol abuse. To examine ethanol sensitivity in rodents, two lines of mice were bred in replicate for high (FAST-1 and -2) and low (SLOW-1 and -2) locomotor stimulant responses to ethanol. After large differences between the lines developed and further response to selection seemed to have arrested, reverse selection was initiated by breeding the slowest FAST mice with each other and the fastest SLOW mice with each other. The reverse-selected lines, named r-FAST and r-SLOW, were virtually equally sensitive to the stimulant effects of the selection dose of ethanol after 16 generations of reverse selection. Methods: These experiments used this unique genetic model to examine two responses, putatively genetically correlated with sensitivity to ethanol stimulation: handling-induced convulsions during chronic ethanol withdrawal, and ethanol-induced hypothermia. Ethanol clearance, for which a small difference was previously found between the FAST and SLOW lines, was also examined. Results: Handling-induced convulsions during chronic ethanol withdrawal were significantly greater in both FAST lines compared with both SLOW lines. Reverse selection eliminated the difference between the replicate 1 lines but did not alter the difference between the replicate 2 lines. Ethanol-induced hypothermia was greater in both SLOW lines compared with the FAST lines. This difference was significantly reduced by reverse selection in r-SLOW mice only. Ethanol clearance rates were similar among all lines and replicates. Conclusions: These data demonstrate the usefulness of reverse-selected lines for examining putatively genetically correlated traits. Changes in the correlated traits demonstrated the existence of persistent trait-relevant genetic heterogeneity and some genetic overlap between the correlated traits and the selection trait. Absence of a change after reverse selection suggests that trait-relevant genetic heterogeneity was eliminated by forward selection or, alternatively, that the trait was not influenced by genes associated with successful reverse selection.

AB - Background: Ethanol sensitivity may be a predictor of genetic predisposition to ethanol abuse. To examine ethanol sensitivity in rodents, two lines of mice were bred in replicate for high (FAST-1 and -2) and low (SLOW-1 and -2) locomotor stimulant responses to ethanol. After large differences between the lines developed and further response to selection seemed to have arrested, reverse selection was initiated by breeding the slowest FAST mice with each other and the fastest SLOW mice with each other. The reverse-selected lines, named r-FAST and r-SLOW, were virtually equally sensitive to the stimulant effects of the selection dose of ethanol after 16 generations of reverse selection. Methods: These experiments used this unique genetic model to examine two responses, putatively genetically correlated with sensitivity to ethanol stimulation: handling-induced convulsions during chronic ethanol withdrawal, and ethanol-induced hypothermia. Ethanol clearance, for which a small difference was previously found between the FAST and SLOW lines, was also examined. Results: Handling-induced convulsions during chronic ethanol withdrawal were significantly greater in both FAST lines compared with both SLOW lines. Reverse selection eliminated the difference between the replicate 1 lines but did not alter the difference between the replicate 2 lines. Ethanol-induced hypothermia was greater in both SLOW lines compared with the FAST lines. This difference was significantly reduced by reverse selection in r-SLOW mice only. Ethanol clearance rates were similar among all lines and replicates. Conclusions: These data demonstrate the usefulness of reverse-selected lines for examining putatively genetically correlated traits. Changes in the correlated traits demonstrated the existence of persistent trait-relevant genetic heterogeneity and some genetic overlap between the correlated traits and the selection trait. Absence of a change after reverse selection suggests that trait-relevant genetic heterogeneity was eliminated by forward selection or, alternatively, that the trait was not influenced by genes associated with successful reverse selection.

KW - Chronic ethanol withdrawal

KW - Ethanol metabolism

KW - Hypothermia

KW - Locomotor stimulation

KW - Reverse Selection

UR - http://www.scopus.com/inward/record.url?scp=0036739879&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036739879&partnerID=8YFLogxK

U2 - 10.1097/00000374-200209000-00003

DO - 10.1097/00000374-200209000-00003

M3 - Article

C2 - 12351925

AN - SCOPUS:0036739879

VL - 26

SP - 1322

EP - 1329

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 9

ER -