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 language | English (US) |
---|---|
Pages (from-to) | 506-517 |
Number of pages | 12 |
Journal | Genes, Brain and Behavior |
Volume | 5 |
Issue number | 7 |
DOIs | |
State | Published - 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