Gonadal hormones affect alcohol drinking, but not cue+yohimbine-induced alcohol seeking, in male and female rats.
Gonadal hormones affect alcohol drinking, but not cue+yohimbine-induced alcohol seeking, in male and female rats.
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DOI：
10.1016/j.physbeh.2017.10.025
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发表时间：
2019-05-01
影响因子：
2.9
通讯作者：
Torregrossa MM
中科院分区：
文献类型：
--
作者：
Bertholomey ML;Torregrossa MM
酒精使用障碍（AUD）是一种慢性、复发性疾病，其特征是饮酒和寻求酒精的不适应模式。虽然AUD的病因存在性别差异，但关于性别相关易感性发展过度酒精动机行为的机制仍有待阐明。虽然大量证据表明循环性腺激素在介导可卡因强化中起着重要作用，但关于乙醇的研究结果却不太一致。至关重要的是，性腺激素对恢复酒精寻求的影响，一种“渴望”式的行为模式，揭示了明显的性别差异，尚未得到检验。因此，本实验的目的是直接比较雄性和雌性大鼠的性腺激素操纵对乙醇驱动行为的影响。大鼠接受假或性腺切除手术，并在手术前或三周内自行给药乙醇，以确定长期高或低性腺激素水平对乙醇饮用的影响。在消失训练期间停止激素治疗，并确定急性注射睾酮（雄性）或雌二醇（雌性）对提示+育亨宾诱导的乙醇寻求恢复的影响。另一组性腺完整的雌性大鼠进行了类似的训练，但测定了抗雌激素药物氟维司汀、选择性雌激素受体调节剂克罗米芬或雌激素受体β拮抗剂PHTPP对乙醇寻求恢复的影响。慢性雌二醇替代显著增加雌性大鼠的乙醇饮用量，而慢性睾酮显著减少雄性大鼠的乙醇饮用量。单独的性腺切除术只产生了适度的饮酒向异性模式的转变，并没有消除无论激素操作如何都存在的强烈的性别差异。先前的慢性和急性激素操作都没有改变线索+育亨宾诱导的乙醇寻找的恢复，尽管雌激素受体的阻断倾向于减少性腺完整的雌性的恢复。总的来说，我们的研究结果表明性激素至少部分介导，但不能完全解释乙醇自我给药的性别差异，循环性激素对乙醇寻求的恢复几乎没有影响。这些结果为进一步研究酒精饮用和寻找的性别差异背后的神经元机制提供了基础。
Alcohol use disorder (AUD) is a chronic, relapsing disease characterized by maladaptive patterns of alcohol drinking and seeking. Though sex differences exist in the etiology of AUD, much remains to be elucidated concerning the mechanisms underlying sex-related vulnerability to developing excessive alcohol-motivated behavior. While a large body of evidence points to an important role of circulating gonadal hormones in mediating cocaine reinforcement, findings are less consistent with respect to ethanol. Critically, the effects of gonadal hormones on the reinstatement of ethanol seeking, a model of “craving”-like behavior that reveals pronounced sex differences, has not yet been examined. Thus, the goal of the present experiment was to directly compare manipulations of gonadal hormones in male and female rats on ethanol-motivated behavior. Rats received sham or gonadectomy surgery with or without hormone replacement prior to and throughout three weeks of operant ethanol self-administration to determine the effects of chronically high or low gonadal hormone levels on ethanol drinking. Hormone treatment ceased during extinction training, and the effects of an acute injection of either testosterone (in males) or estradiol (in females) on cue+yohimbine-induced reinstatement of ethanol seeking was determined. Separate groups of gonadally- intact female rats went through similar training, but the effects of either the antiestrogen, fulvestrant, the selective estrogen receptor modulator, clomiphene, or the estrogen receptor β antagonist, PHTPP, on the reinstatement of ethanol seeking were determined. Chronic estradiol replacement produced significant increases in ethanol drinking in female rats, while chronic testosterone significantly decreased ethanol drinking in male rats. Gonadectomy alone only produced modest shifts in drinking towards the opposite-sex pattern, and did not eliminate the robust sex differences that persisted regardless of hormone manipulations. Neither prior chronic nor acute hormone manipulations altered cue+yohimbine-induced reinstatement of ethanol seeking, though blockade of estrogen receptors tended to reduce reinstatement in gonadally- intact females. Overall, our findings indicate that gonadal hormones at least partially mediate, but do not totally account for the sex differences evident in ethanol self-administration, and circulating gonadal hormones have little effect on the reinstatement of ethanol seeking. These results provide a foundation for future studies examining the neuronal mechanisms underlying sex differences in ethanol drinking and seeking.
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影响因子：
2.7
作者：
Bertholomey, Megan L.;Verplaetse, Terril L.;Czachowski, Cristine L.
通讯作者：
Czachowski, Cristine L.
影响因子：
7.4
作者：
Arnold, Arthur P.;Chen, Xuqi
通讯作者：
Chen, Xuqi
影响因子：
2.5
作者：
Ajdzanovic, Vladimir;Jaric, Ivana;Milosevic, Verica
通讯作者：
Milosevic, Verica
DOI：
10.1621/nrs.06008
发表时间：
2008-06-27
期刊：
Nuclear receptor signaling
影响因子：
--
作者：
Claessens F;Denayer S;Van Tilborgh N;Kerkhofs S;Helsen C;Haelens A
通讯作者：
Haelens A
影响因子：
2.3
作者：
Anker, Justin J.;Larson, Erin B.;Carroll, Marilyn E.
通讯作者：
Carroll, Marilyn E.