Region-specific down-regulation of Crhr1 gene expression in alcohol-preferring msP rats following ad lib access to alcohol.
Corticotropin-releasing hormone 1 receptors (CRH-R1) mediate increased behavioral sensitivity to stress and excessive alcohol self-administration following a history of dependence. It was recently demonstrated that the genetically selected alcohol-preferring msP rat line replicates many characteristics of the post-dependent state, due to an innate up-regulation of the Crhr1 transcript in several limbic areas related to alcohol drinking motivation. Here, we examined whether voluntary alcohol consumption might be able to down-regulate Crhr1 transcript levels in msP rats in brain areas where elevated expression previously has been shown. Within central and medial amygdala (CeA, MeA), as well as the Nc. Accumbens, 2 weeks'ad lib access to alcohol led to a highly significant down-regulation of the Crhr1 transcript. Alcohol-induced Crhr1 down-regulation was not seen in cingulate cortex. These data support that recruitment of CRH-R1 signaling within components of the extended amygdala drives excessive alcohol intake, and that alcohol is voluntarily consumed in part for its ability to reduce CRH-R1 activity in this region.
Hansson
Anita C
AC
Laboratory of Clinical and Translational Studies, NIAAA/NIH, Bethesda, MD 20892-1108, USA.
Cippitelli
Andrea
A
Sommer
Wolfgang H
WH
Ciccocioppo
Roberto
R
Heilig
Markus
M
D000437:Alcoholism / Q000235:genetics*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D006179:Gyrus Cinguli / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1