Corticotropin-releasing factor gene expression is down-regulated in the central nucleus of the amygdala of alcohol-preferring rats which exhibit high anxiety: a comparison between rat lines selectively bred for high and low alcohol preference.
The role of amygdaloid corticotropin-releasing factor (CRF) in alcoholism is not clear. Alcohol-preferring (P) rats and high alcohol-drinking (HAD) rats are selectively bred for high alcohol preference, and have been considered suitable animal models for studying alcoholism. The CRF neurons in the central nucleus of the amygdala (CeA) of P rats and HAD rats were studied in comparison with those of their respective counterparts, namely, alcohol-nonpreferring (NP) rats and low alcohol-drinking (LAD) rats. Specifically, CRF-immunoreactivity (ir) in the CeA and paraventricular hypothalamic nucleus (PVN) was assessed using radioimmunohistochemical (RIH) assay in alcohol-naive P/NP rats, and HAD/LAD rats. Furthermore, CRF mRNA was examined using in situ hybridization in the CeA of P/NP rats. Anxiety levels were also evaluated using an elevated plus maze. Results of the present study showed that CRF-ir was significantly lower in the CeA of P rats than NP rats. Moreover, CRF mRNA in the CeA was also much lower in P rats than NP rats. Such differences were not seen in the PVN. Interestingly, those P rats exhibited higher anxiety than NP rats. In contrary, there were no innate differences of CRF-ir in both the CeA and PVN between HAD and LAD rats whose anxiety levels were similar. This study is consistent with the literature showing CRF knockout (KO) induces alcohol drinking, and central administrations of CRF reduce alcohol intake. Collectively, the present study suggests that reduced CRF gene expression in the CeA of P rats is associated with their alcohol preference and anxiety.
Hwang
Bang H
BH
Department of Anatomy & Cell Biology (MS-5035), Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA. bhwang@iupui.edu
Stewart
Robert
R
Zhang
Jing-Kang
JK
Lumeng
L
L
Li
T-K
TK
D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000679:Amygdala / Q000033:anatomy & histology / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D002452:Cell Count / Q000379:methods; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012641:Selection, Genetic
D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone