壓力的增加可能導(dǎo)致大腦神經(jīng)信號的匯聚,，觸發(fā)促腎上腺皮質(zhì)激素釋放因子（CRF）的釋放。而這又會引發(fā)激活身體對于壓力的緊急自主和行為響應(yīng)的分子的釋放,，后者是由CRH基因編碼到。但是太多的CRH神經(jīng)遞質(zhì)可能導(dǎo)致諸如抑郁癥,、創(chuàng)傷后應(yīng)激障礙以及酒精依賴等疾病,。在大鼠身上，CRF肽系統(tǒng)的過度激活導(dǎo)致了更高的酒精攝入。
Christina Barr及其同事調(diào)查了CRH基因的一個突變是否會對在幼年時接觸到壓力的成年獼猴的酒精使用產(chǎn)生影響,。這組作者發(fā)現(xiàn),，攜帶T版本（在獼猴身上發(fā)現(xiàn)的啟動子單核苷多態(tài)）的這種基因的獼猴比攜帶“C”版本等位基因的獼猴在壓力下表現(xiàn)得更焦慮。這組作者也證明了那些攜帶T版本的猴子比攜帶C突變的猴子具有更高水平的這種壓力基因和更高的酒精攝入,。這組作者提出,，CRH基因突變可能充當(dāng)酒精濫用或早發(fā)型酒癮的風(fēng)險因子。
這組科學(xué)家說,，阻斷CRH活動的藥物可以作為治療酒精依賴的一種療法,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS August 17, 2009, doi: 10.1073/pnas.0902863106
Functional CRH variation increases stress-induced alcohol consumption in primates
Christina S. Barra,1,2, Rachel L. Dvoskina,1, Manisha Guptea,b, Wolfgang Sommera, Hui Suna, Melanie L. Schwandta, Stephen G. Lindella, John W. Kasckowc, Stephen J. Suomid,1, David Goldmanb,1, J. Dee Higleye,1 and Markus Heiliga,1
aLaboratory of Clinical and Translational Studies and
bLaboratory of Neurogenetics, National Institutes of Health/National Institutes on Alcohol Abuse and Alcoholism, Bethesda, MD 20892;
cVA Pittsburgh Health Care System MIRECC and Behavioral Health and Western Psychiatric Institute and Clinics, University of Pittsburgh Medical Center Western Psychiatric Institute and Clinics, University of Pittsburgh Medical Center, Pittsburgh, PA 15206;
eDepartment of Psychology, Brigham Young University, 1042 SWKT, Provo, UT, 84602; and
dLaboratory of Comparative Ethology, National Institutes of Health/National Institute of Child Health and Human Development, Poolesville, MD, 20837
Corticotropin-releasing factor (CRF), encoded by the CRH gene, is a key integrator of stress responses, and, as such, CRH gene variation may contribute to individual differences in susceptibility to stress-related pathology. In rhesus macaques, a single nucleotide polymorphism (SNP) is found within the CRH promoter (?248C→ T). Here, we assessed whether this variant influenced stress responding and, because increased CRF system activity drives alcohol drinking in rodents, we examined whether it predicted voluntary alcohol consumption as a function of prior stress exposure. Using a hypothalamic nuclear extract, we showed that the ?248 T allele resulted in increased DNA protein interactions relative to the C allele. In vitro, the T allele resulted in CRH promoter activity that was higher following both stimulation with forskolin and treatment with dexamethasone. Endocrine and behavioral responses to social separation stress (release of ACTH and cortisol, and suppression of environmental exploration, respectively) were higher among carriers of the T allele, particularly among those exposed to early adversity in the form of peer rearing. We also found that T allele carriers with a history of early life adversity consumed more alcohol in a limited-access paradigm. Our data suggest that CRH promoter variation that confers increased stress reactivity increases the risk for alcohol use disorders in stress-exposed individuals.
