Almeida O F, Shoaib M, Deicke J, Fischer D, Darwish M H, Patchev V K
Neuroadaptations Group, Department of Neuroendocrinology, Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
J Clin Invest. 1998 Jun 15;101(12):2677-85. doi: 10.1172/JCI1198.
An ethanol oral self administration paradigm showed the existence of gender differences in alcohol preference in rats: whereas males and females initiated alcohol drinking at similar rates, females maintained their preference for ethanol over a longer duration. Neonatal estrogenization of females, which effectively confers a male phenotype on a genetically female brain, resulted in patterns of drinking that were similar to those displayed by intact male rats, indicating that gender differences in alcohol drinking patterns may be, at least partially, accounted for by sexual differentiation of the brain. To test whether gonadal steroids also exert activational effects on ethanol-seeking behavior, we also examined the effects of gonadectomy alone, or in combination with gonadal steroid replacement therapy. Castration did not significantly alter ethanol consumption in males, although treatment of castrated rats with dihydrotestosterone resulted in a significant inhibition of this parameter. As compared with the situation in intact female rats, ethanol ingestion was significantly reduced in ovariectomized female rats receiving estradiol (E2) and in ovariectomized female rats receiving combined E2 and progesterone replacement therapy. However, neither ovariectomy nor progesterone replacement in ovariectomized rats resulted in ethanol drinking patterns that were different compared to those observed in intact female controls. Thus, dihydrotestosterone and E2, respectively, appear to exert modulatory influences on the male and female rats' preference for ethanol, but further investigations are necessary to determine to what extent these effects result from activational actions on the brain.
一项乙醇口服自我给药范式显示,大鼠在酒精偏好方面存在性别差异:虽然雄性和雌性开始饮酒的速率相似,但雌性对乙醇的偏好持续时间更长。对雌性进行新生期雌激素化,这有效地使基因上为雌性的大脑具有雄性表型,导致其饮酒模式与完整雄性大鼠相似,这表明饮酒模式的性别差异可能至少部分是由大脑的性分化造成的。为了测试性腺类固醇是否也对寻求乙醇的行为产生激活作用,我们还研究了单独去势或联合性腺类固醇替代疗法的效果。去势并未显著改变雄性大鼠的乙醇摄入量,尽管用二氢睾酮治疗去势大鼠会导致该参数显著降低。与完整雌性大鼠的情况相比,接受雌二醇(E2)的去卵巢雌性大鼠和接受E2与孕酮联合替代疗法的去卵巢雌性大鼠的乙醇摄入量显著减少。然而,去卵巢以及去卵巢大鼠的孕酮替代均未导致其饮酒模式与完整雌性对照大鼠观察到的不同。因此,二氢睾酮和E2似乎分别对雄性和雌性大鼠对乙醇的偏好产生调节作用,但需要进一步研究以确定这些影响在多大程度上是由对大脑的激活作用导致的。