• Crabbe, John Jr (PI)

Project: Research project

Project Details


The importance of genotypic differences in the susceptibility to alcoholism
in man, and their influence on ethanol sensitivity, tolerance, and
withdrawal severity in animals, is achieving ever greater recognition.
While we know that susceptibility to almost all aspects of alcohol's
effects in animals is to some degree inherited, we have little idea yet
what specifically is inherited. The proposed research will provide an animal genetic model for an unique
biochemical and behavioral response to ethanol that will allow us to
unravel some of the genetic relationships among different aspects of
ethanol responsiveness. The proposed project will develop lines of mice
that differ genetically in their sensitivity to ethanol's effect to
stimulate activity in an open field. Using within-family selective
breeding, two Activity Prone (ACP) and two Activity Resistant (ACR) lines
will be developed. The existence of replicate lines will allow clear
differentiation of correlated responses to selection from those arise
between the given pair of ACP and ACR lines by chance. Methods will be
adopted to insure that the lines differ in activity sensitivity to the same
brain level of ethanol. The major long-term goal of the proposed selective breeding study is to
shed light on an ubiquitous, easily assessed response to ethanol (activity)
that potentially mimics biochemical and behavioral indices of the
euphoriant response in man. Previous research has identified
ethanol-induced activity as a key response that is: (1) easily measured;
(2) has clear dose-effect and temporal characteristics; (3) is genetically
mediated; (4) may serve as a biochemical and behavioral model for ethanol's
behavioral stimulant and euphoriant effects in man; and (5) does not appear
to display tolerance development. The successful selection of the proposed
lines will provide a unique genetic model for the behaviorally-stimulating
effects of ethanol.
Effective start/end date5/1/8511/30/91


  • National Institutes of Health: $161,135.00


  • Medicine(all)


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