Richter R M, Zorrilla E P, Basso A M, Koob G F, Weiss F
Department of Molecular Neurobiology, Institute of Molecular Pharmacology, Berlin, Germany.
Alcohol Clin Exp Res. 2000 Dec;24(12):1765-72.
Dysregulation of the stress-regulatory corticotropin-releasing factor (CRF) system in the central nucleus of the amygdala (CeA) may be a factor in genetically determined alcohol preference.
To test this hypothesis, basal and restraint stress-induced CRF efflux in the CeA was determined by microdialysis in Sardinian alcohol-preferring (sP) and nonpreferring (sNP) rats. In addition, differences in anxiety-like behavior between sP and sNP rats were evaluated by using the elevated plus maze and conditioned defensive burying tests.
Basal dialysate CRF levels in the CeA were elevated in the alcohol-preferring line (sP, 281.2+/-83.96 pg/ml; sNP, 70.2+/-16.76 pg/ml; p < 0.05). In contrast, no differences in whole-tissue CRF content in the CeA were observed (sP, 1143+/-142 ng/mg protein; sNP, 1181+/-139 ng/mg protein). Restraint stress elevated CRF dialysate concentrations in both sP and sNP rats. Rats of the sP line exhibited more anxiety-like behavior than sNP rats in the elevated plus maze but not in the conditioned defensive burying test.
The results suggest that ethanol-preferring sP rats show a dysregulation in basal CRF release within the CeA that may, in turn, heighten ethanol intake and increase susceptibility to anxiogenic stimuli in these animals.
杏仁核中央核（CeA）中应激调节促肾上腺皮质激素释放因子（CRF）系统的失调可能是遗传决定的酒精偏好的一个因素。
为了验证这一假设，通过微透析法测定了撒丁岛酒精偏好（sP）和非偏好（sNP）大鼠CeA中基础和束缚应激诱导的CRF流出量。此外，通过高架十字迷宫和条件性防御埋埋试验评估了sP和sNP大鼠之间焦虑样行为的差异。
酒精偏好品系的CeA中基础透析液CRF水平升高（sP，281.2±83.96 pg/ml；sNP，70.2±16.76 pg/ml；p<0.05）。相比之下，CeA中全组织CRF含量未观察到差异（sP，1143±142 ng/mg蛋白质；sNP，1181±139 ng/mg蛋白质）。束缚应激使sP和sNP大鼠的CRF透析液浓度均升高。在高架十字迷宫中，sP品系的大鼠比sNP大鼠表现出更多的焦虑样行为，但在条件性防御埋埋试验中则不然。
结果表明，偏好乙醇的sP大鼠在CeA内基础CRF释放存在失调，这反过来可能会增加这些动物的乙醇摄入量，并增加其对焦虑源刺激的易感性。
