This proposal is designed to address the possible genetic relationships between the locomotor stimulant effects of ethanol and those of allopregnanolone. We have already analyzed the locomotor stimulant effects of these two compounds in the BXD recombinant inbred mouse set, and identified a statistically significant correlation between the locomotor response to ethanol and locomotor response to allopregnanolone. This analysis has identified a number of provisional quantitative train loci for response to allopregnanolone, some of which are regions known to contain loci for ethanol traits. Here we propose to extend upon these, findings by generating an F2 population which will allow us to confirm or reject these provisional QTLs. Additionally, we will examine locomotor response to allopregnanolone in FAST and SLOW mice selected for their high and low locomotor response to ethanol in order to determine whether selection has favored similar responses to allopregnanolone. We will also determine whether cross sensitization exists between ethanol and allopregnanolone. Finally, we will test finasteride's ability to antagonize the locomotor stimulant effects of ethanol.
|Meyer, P J; Palmer, A A; McKinnon, C S et al. (2005) Behavioral sensitization to ethanol is modulated by environmental conditions, but is not associated with cross-sensitization to allopregnanolone or pentobarbital in DBA/2J mice. Neuroscience 131:263-73|
|Bergstrom, Hadley C; Palmer, Abraham A; Wood, Robin D et al. (2003) Reverse selection for differential response to the locomotor stimulant effects of ethanol provides evidence for pleiotropic genetic influence on locomotor response to other drugs of abuse. Alcohol Clin Exp Res 27:1535-47|
|Palmer, Abraham A; Low, Malcolm J; Grandy, David K et al. (2003) Effects of a Drd2 deletion mutation on ethanol-induced locomotor stimulation and sensitization suggest a role for epistasis. Behav Genet 33:311-24|
|Palmer, Abraham A; Breen, Laura L; Flodman, Pamela et al. (2003) Identification of quantitative trait loci for prepulse inhibition in rats. Psychopharmacology (Berl) 165:270-9|
|Palmer, Abraham A; McKinnon, Carrie S; Bergstrom, Hadley C et al. (2002) Locomotor activity responses to ethanol, other alcohols, and GABA-A acting compounds in forward- and reverse-selected FAST and SLOW mouse lines. Behav Neurosci 116:958-67|
|Palmer, Abraham A; Phillips, Tamara J (2002) Effect of forward and reverse selection for ethanol-induced locomotor response on other measures of ethanol sensitivity. Alcohol Clin Exp Res 26:1322-9|
|Palmer, Abraham A; Moyer, Michelle R; Crabbe, John C et al. (2002) Initial sensitivity, tolerance and cross-tolerance to allopregnanolone- and ethanol-induced hypothermia in selected mouse lines. Psychopharmacology (Berl) 162:313-22|