Genetic variation in 3alpha,5alpha-THP levels influences sensitivity to the behavioural effects of ethanol in BXD recombinant inbred mice (Abstract/Poster in atti di convegno)

Type
Label
  • Genetic variation in 3alpha,5alpha-THP levels influences sensitivity to the behavioural effects of ethanol in BXD recombinant inbred mice (Abstract/Poster in atti di convegno) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Alternative label
  • Beattie M, Porcu P, Carlson SL, O'Buckley TK, Hodge CW and Morrow AL (2014)
    Genetic variation in 3alpha,5alpha-THP levels influences sensitivity to the behavioural effects of ethanol in BXD recombinant inbred mice
    in 44th Annual Meeting Society for Neuroscience, Washington, DC, USA, 15-19 November 2014
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Beattie M, Porcu P, Carlson SL, O'Buckley TK, Hodge CW and Morrow AL (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#titoloVolume
  • 2014 Neuroscience Meeting Planner (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#volumeInCollana
  • Program No. 324.19 (literal)
Note
  • Poster (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • UNC Chapel Hill, Chapel Hill, NC? Natl. Res. Council (CNR) Neurosci. Inst., Cagliari, Italy (literal)
Titolo
  • Genetic variation in 3alpha,5alpha-THP levels influences sensitivity to the behavioural effects of ethanol in BXD recombinant inbred mice (literal)
Abstract
  • Sensitivity to ethanol is thought to be a key risk factor for alcoholism. Ethanol sensitivity is influenced by GABAergic neuroactive steroids in Sprague Dawley rats and humans. Using 40 BxD recombinant inbred (RI) strains derived from an intercross of the C57BL/6J and DBA/2J strains, we found dramatic genetic variation in basal deoxycorticosterone (DOC) levels in both cerebral cortex and plasma (Porcu et al., 2011). Ten strains were selected across the range of variation in DOC levels and tested for genetic variation in ethanol-induced changes in olfactory bulb and tubercle (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP) levels. Ethanol responses ranged from -28% in BxD16 mice to +65% in BxD27 mice. No effect of ethanol was observed in C57BL/6J mice. Therefore, these three strains were utilized to explore behavioral responses to acute ethanol administration. The mice (n=8/strain) were administered saline or ethanol (i.p.) and loss of righting reflex (LORR), locomotor response, bicuculline seizure threshold, and mRNA levels of the neuroactive steroid biosynthetic enzyme 5alpha-reductase (5alpha-R) were examined. Ethanol-induced duration of loss of righting reflex (LORR) is approximately 3-fold greater in BxD 16 mice at both 3.5 and 4g/kg ethanol compared to BxD 27 and C57BL/6J mice (F(2,26)=49.8, p<0.0001). In the open-field test, ethanol (3g/kg) reduced the total distanced traveled by 95±3.2% (Tukey, p<0.05) in BxD 16 mice, but increased the total distance traveled in BxD 27 mice by 307±121% (Tukey, p<0.05), and had no effect in C57BL/6J mice (F(6,84)=5.8, p<0.0001). Ethanol administration (2g/kg) increased bicuculline seizure thresholds in all strains, but BxD16 mice were 75% less sensitive to ethanol than C57BL/6J or BxD27 mice (F(2,24)=4.9, p<0.05). Ethanol increased 5alpha-R mRNA in the olfactory bulb and tubercle by 17±3% (p<0.01) in BxD27 mice, which may explain increased brain 3alpha,5alpha-THP levels in that strain. No effect of ethanol on 5alpha-R mRNA was observed in the other strains. These data indicate that genetic variation in ethanol-induced 3alpha,5alpha-THP levels may contribute to specific behavioral effects of ethanol. Further studies are required to understand how ethanol-induced alterations of neuroactive steroids underlie ethanol sensitivity across BxD strains. (literal)
Prodotto di
Autore CNR

Incoming links:


Prodotto
Autore CNR di
data.CNR.it