Sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone: A quantitative trait locus study of common genetic influence

A. A. Palmer, C. N. Lessov-Schlaggar, C. A. Ponder, C. S. McKinnon, T. J. Phillips

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Previous studies have suggested that common genetic mechanisms influence sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone. We conducted two quantitative trait locus (QTL) studies to identify chromosomal regions that harbor genes that influence locomotor response to ethanol (2 g/kg) and allopregnanolone (17 mg/kg) using F2 crosses between C57BL/6J and DBA/2J mice. Because our previous data from the BXD recombinant inbred strains had indicated that chromosome 2 contained QTL for sensitivity to the locomotor-stimulant effects of both ethanol and allopregnanolone, we also tested reciprocal chromosome 2 congenic strains for sensitivity to the locomotor-stimulant effects of both drugs. The F2 analysis for ethanol sensitivity identified significant QTL on chromosomes 1 and 2 and suggestive QTL on chromosomes 5 and 9. The analysis of the allopregnanolone F2 study identified suggestive QTL on chromosomes 3, 5 and 12. Suggestive evidence for a female-specific QTL on chromosome 2 was also found. The studies of congenic mouse strains indicated that both the congenic strains captured one or more QTL for sensitivity to the locomotor-stimulant effects of both ethanol (2 g/kg) and allopregnanolone (17 mg/kg). When Fisher's method was used to combine the P values for the RI, F2 and congenic studies of the chromosome 2 QTL, cumulative probability scores of 9.6 × 10 -15 for ethanol and 7.7 × 10-7 for allopregnanolone were obtained. These results confirm the presence of QTL for ethanol and allopregnanolone sensitivity in a common region of chromosome 2 and suggest possible pleiotropic genetic influence on sensitivity to these drugs.

Original languageEnglish (US)
Pages (from-to)506-517
Number of pages12
JournalGenes, Brain and Behavior
Volume5
Issue number7
DOIs
StatePublished - Oct 2006

Keywords

  • 3α,5α- tetrahydroprogesterone
  • 3α-Hydroxy-5α-pregnan-20-one
  • Alcohol
  • Allopregnanolone
  • Ethanol
  • GABA
  • Genetic
  • Locomotor
  • Mouse
  • Neurosteroid
  • QTL

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience

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