BACKGROUND: The DBA/2J (D2) and C57BL/6J (B6) @entity19 strains are the most widely studied genetic models of severe and mild acute @entity167 withdrawal, respectively. Previous studies have identified quantitative trait loci and genes involved in risk for acute @entity1068 withdrawal using mapping populations derived from the D2 and B6 strains, but the brain region(s) and circuit(s) by which these genes and their protein products influence @entity1068 physiological dependence and associated withdrawal remain to be elucidated. METHODS: B6 and D2 were administered a sedative-hypnotic dose of @entity1068 (4 g/kg) or saline (control) and returned to their home cages where they were left undisturbed for 7 hr, which has been shown in previous studies to correspond to peak acute @entity1068 withdrawal severity. The @entity19 were then euthanized and assessed for their numbers of @entity9830 immunoreactive neurons across 26 brain regions. The question addressed was whether or not @entity1068 -withdrawn D2 and B6 @entity19 differed in @entity9830 induction (neural activation) within circuitry that could explain the severe @entity1068 withdrawal of the D2 strain and the mild @entity1068 withdrawal in B6 strain @entity19 . RESULTS: At peak acute @entity1068 -withdrawal @entity1068 -withdrawn D2 and B6 @entity19 differed in neural activation within the basal ganglia, including the subthalamic nucleus and the two major output nuclei of the basal ganglia (the medial globus pallidus and the substantia nigra pars reticulata). Genotype-dependent @entity9830 induction was also apparent in associated circuitry including the lateral septum, the ventral tegmental area, the nucleus accumbens core, the dorsolateral caudate putamen, the substantia nigra pars compacta, the cingulate and entorhinal cortices, and the ventral pallidum. D2 and B6 @entity19 showed comparable neural activation in the bed nucleus of the stria terminalis, and the nucleus accumbens shell. CONCLUSIONS: The present studies are the first to use immediate early gene product expression to assess the pattern of neural activation associated with acute @entity1068 withdrawal. Our results point to the involvement of an extended basal ganglia circuit in genetically determined differences in acute @entity1068 withdrawal. Based on these data, we suggest that quantitative trait genes (QTGs) involved in acute @entity1068 withdrawal exert their effects on this phenotype via one or more of the brain regions and circuits identified. As more information becomes available that integrates neural circuit and QTG analyses, the precise mechanisms by which QTGs affect @entity1068 physiological dependence and associated withdrawal will become apparent.

Acute XXXX withdrawal is associated with @entity9830 expression in the basal ganglia and associated circuitry: C57BL/6J and DBA/2J inbred @entity19 strain analyses.

@entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity9830 :: ('14281(Tax:10090)', 'Gene') :: ['c-Fos'] @entity167 :: ('CHEBI:16236', 'Chemical') :: ['alcohol'] @entity1068 :: ('MESH:D000431', 'Chemical') :: ['ethanol']
@entity167 :: (CHEBI:16236,Chemical) :: ['alcohol']
