Abstract

It is proposed to conduct investigations to utilize and further characterize newly developed genetic lines of mice which have been selectively-bred for either increased or decreased handling-induced convulsions (HIC) following withdrawal from ethanol (WSP and WSR lines). It is planned to determine if these genetically-based differences in susceptibility to HIC associated with physical dependence on ethanol are genetically related to susceptibility (cross-susceptibility) to HIC and other withdrawal signs associated with physical dependence on t-butanol, nitrous oxide, phenobarbital, diazepam and morphine. If so, then this would suggest that the mechanisms responsible for the intensity of HIC following ethanol withdrawal are also operative with these other drugs and/or withdrawal signs. Conversely, if ethanol HIC susceptibility does not generalize to these other drugs and/or withdrawal signs monitored, then independent controlling mechanisms are implicated. In summary, the development of these selected lines now allows a novel approach to be utilized to determine the degree of commonality that exists among a number of drug dependencies with respect to alcohol.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA006243-03
Application #
3109445
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of North Dakota
Department
Type
Schools of Medicine
DUNS #
102280781
City
Grand Forks
State
ND
Country
United States
Zip Code
58202

  Publications

Metten, Pamela; Iancu, Ovidiu D; Spence, Stephanie E et al. (2014) Dual-trait selection for ethanol consumption and withdrawal: genetic and transcriptional network effects. Alcohol Clin Exp Res 38:2915-24
Metten, Pamela; Sorensen, Michelle L; Cameron, Andy J et al. (2010) Withdrawal severity after chronic intermittent ethanol in inbred mouse strains. Alcohol Clin Exp Res 34:1552-64
Crabbe, John C; Phillips, Tamara J; Belknap, John K (2010) The complexity of alcohol drinking: studies in rodent genetic models. Behav Genet 40:737-50
Metten, Pamela; Crabbe, John C; Belknap, John K (2009) Genetic correlates of morphine withdrawal in 14 inbred mouse strains. Drug Alcohol Depend 99:123-31
Chen, Gang; Reilly, Matthew T; Kozell, Laura B et al. (2009) Differential activation of limbic circuitry associated with chronic ethanol withdrawal in DBA/2J and C57BL/6J mice. Alcohol 43:411-20
Kozell, L; Belknap, J K; Hofstetter, J R et al. (2008) Mapping a locus for alcohol physical dependence and associated withdrawal to a 1.1 Mb interval of mouse chromosome 1 syntenic with human chromosome 1q23.2-23.3. Genes Brain Behav 7:560-7
Belknap, John K; Metten, Pamela; Beckley, Ethan H et al. (2008) Multivariate analyses reveal common and drug-specific genetic influences on responses to four drugs of abuse. Trends Pharmacol Sci 29:537-43
Hofstetter, J R; Hitzemann, R J; Belknap, J K et al. (2008) Characterization of the quantitative trait locus for haloperidol-induced catalepsy on distal mouse chromosome 1. Genes Brain Behav 7:214-23
Metten, Pamela; Buck, Kari J; Merrill, Catherine M et al. (2007) Use of a novel mouse genotype to model acute benzodiazepine withdrawal. Behav Genet 37:160-70
Peirce, Jeremy L; Li, Hongqiang; Wang, Jintao et al. (2006) How replicable are mRNA expression QTL? Mamm Genome 17:643-56

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