Effects of aromatase inhibition and androgen activity on serotonin and behavior in male macaques.
Effects of aromatase inhibition and androgen activity on serotonin and behavior in male macaques.
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DOI：
10.1037/a0032016
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发表时间：
2013-06
影响因子：
1.9
通讯作者：
Coleman, Kristine
中科院分区：
文献类型：
--
作者：
Bethea, Cynthia L.;Reddy, Aruba La P.;Robertson, Nicola;Coleman, Kristine
人类和动物的攻击性与雄激素和血清素功能有关。为了进一步了解雄激素对雄性猕猴血清素和攻击性的影响，我们试图操纵循环雄激素和芳香酶的活性。然后确定行为和血清素的内源可用性。雄性日本猕猴 (Macaca fuscata) 被阉割 5-7 个月，然后用 [1] 安慰剂、[2] 睾酮 (T)、[3] T+度他雄胺（5a 还原酶抑制剂；AvodartTM）、[4] T+来曲唑（非类固醇芳香酶抑制剂；FemeraTM）、[5] Flutamide+ATD（雄激素拮抗剂加类固醇）治疗 3 个月。芳香酶抑制剂）或[6]二氢睾酮（DHT）+ATD（n=5/组）。在治疗期间进行行为观察。治疗期结束时，每只动物用异丙酚镇静，并推注芬氟拉明（5 mg/kg）。芬氟拉明引起与内源性可用性成比例的血清素释放，反过来，血清素刺激催乳素的分泌。因此，血清催乳素浓度反映了内源性血清素。芬氟拉明显着增加所有组中的血清素/催乳素（p <0.0001）。 T 治疗组中芬氟拉明诱导的血清素/催乳素显着高于其他组 (p<0.0001)。去势部分降低了血清素/催乳素反应；来曲唑部分阻断T的作用。用ATD（一种非竞争性抑制剂）完全抑制芳香酶，在存在或不存在DHT的情况下，显着且类似地降低芬氟拉明诱导的血清素/催乳素反应。攻击行为和打哈欠（雄激素活性的指标）均与血清素/催乳素无关，但假定芳香酶活性与催乳素显着相关（p <0.0008；r2 = 0.95）。总之，雄激素会诱发攻击行为，但不会调节血清素。总而言之，数据表明芳香酶活性支持血清素的产生，而雄激素通过另一种机制增加攻击性。
Aggression in humans and animals has been linked to androgens and serotonin function. To further our understanding of the effect of androgens on serotonin and aggression in male macaques, we sought to manipulate circulating androgens and the activity of aromatase; and to then determine behavior and the endogenous availability of serotonin. Male Japanese macaques (Macaca fuscata) were castrated for 5-7 months and then treated for 3 months with [1] placebo, [2] testosterone (T), [3] T+Dutasteride (5a reductase inhibitor; AvodartTM), [4] T+Letrozole (non-steroidal aromatase inhibitor; FemeraTM), [5] Flutamide+ATD (androgen antagonist plus steroidal aromatase inhibitor) or [6] dihydrotestosterone (DHT)+ATD (n=5/group). Behavioral observations were made during treatments. At the end of the treatment period, each animal was sedated with propofol and administered a bolus of fenfluramine (5 mg/kg). Fenfluramine causes the release of serotonin proportional to endogenous availability and in turn, serotonin stimulates the secretion of prolactin. Therefore, serum prolactin concentrations reflect endogenous serotonin. Fenfluramine significantly increased serotonin/prolactin in all groups (p <0.0001). Fenfluramine-induced serotonin/prolactin in the T-treated group was significantly higher than the other groups (p<0.0001). Castration partially reduced the serotonin/prolactin response; and Letrozole partially blocked the effect of T. Complete inhibition of aromatase with ATD, a non-competitve inhibitor, significantly and similarly reduced the fenfluramine-induced serotonin/prolactin response in the presence or absence of DHT. Neither aggressive behavior nor yawning (indicators of androgen activity) correlated with serotonin/prolactin, but posited aromatase activity correlated significantly with prolactin (p<0.0008; r2 =0.95). In summary, androgens induced aggressive behavior but they did not regulate serotonin. Altogether, the data suggest that aromatase activity supports serotonin production and that androgens increase aggression by another mechanism.
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影响因子：
0.7
作者：
Chichinadze, K. N.;Domianidze, T. R.;Lazarashvili, A. G.
通讯作者：
Lazarashvili, A. G.
影响因子：
5.3
作者：
Goedhard, Laurette E.;Stolker, Joost J.;Egberts, Toine C. G.
通讯作者：
Egberts, Toine C. G.
影响因子：
3.5
作者：
EATON, GG;WORLEIN, JM;GLICK, BB
通讯作者：
GLICK, BB
影响因子：
3.4
作者：
Abel, KM;Cleare, AJ
通讯作者：
Cleare, AJ
影响因子：
11.3
作者：
COCCARO, EF;LAWRENCE, T;SIEVER, LJ
通讯作者：
SIEVER, LJ