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Elevated GABA levels in the medial prefrontal cortex and lower estrogen levels abolish cocaine sensitization behavior in ovariectomized female rats
Brain Research ( IF 2.7 ) Pub Date : 2020-10-07 , DOI: 10.1016/j.brainres.2020.147144
Luana Freese 1 , Marilise Fraga de Souza 1 , Maurício Schüler Nin 2 , Greice Calleti 3 , Valéria Flores Peres 1 , Rosane Gomez 4 , Helena Maria Tannhauser Barros 5
Affiliation  

Animal models show that cocaine sensitization, a behavioral marker of addiction, is more significant in intact gonadal female than male rats and ovariectomy suppress this behavior in female rats. However, few studies explore changes in neurotransmission related to this phenomenon. Here we investigated the in vivo changes on GABA, glutamate, and taurine levels in the medial prefrontal cortex (mPFC) of gonadal intact or ovariectomized female rats after a cocaine challenge administration. Adult female rats were bilaterally ovariectomized (OVX), or sham-operated (SHAM) and randomly assigned to control (CTR), acute (ACT), or repeated (RPT) cocaine administration groups. In the challenge day, after eight days of daily cocaine (15 mg/kg) or saline administration and ten days of washout and stereotaxic surgery, RPT and ACT groups received cocaine, and the CTR group received saline. Horizontal locomotion was monitored concomitantly with microdialysate collection to determine extracellular GABA, glutamate, and taurine levels. Hormonal determination in blood samples confirmed the lower hormonal status of the OVX. Cocaine sensitization occurred in SHAM-RPT female rats after the challenge administration. Non-sensitized OVX-RPT rats showed a peak of GABA at 30 min after cocaine administration, with no change on glutamate and taurine levels. Therefore, elevated GABA levels in the mPFC and lower serum estrogen levels abolish cocaine sensitization behavior in ovariectomized female rats. We discuss some possible implications of these finding for future models of cocaine sensitization research lighting in the female hormonal influence.



中文翻译:

内侧前额叶皮层中 GABA 水平升高和雌激素水平降低消除了去卵巢雌性大鼠的可卡因致敏行为

动物模型表明,可卡因致敏是成瘾的一种行为标志物,在完整性腺雌性大鼠中比雄性大鼠更显着,卵巢切除术抑制了雌性大鼠的这种行为。然而,很少有研究探讨与这种现象相关的神经传递变化。在这里,我们研究了体内在可卡因激发给药后,性腺完整或卵巢切除的雌性大鼠的内侧前额叶皮层 (mPFC) 中 GABA、谷氨酸和牛磺酸水平的变化。成年雌性大鼠双侧卵巢切除 (OVX) 或假手术 (SHAM) 并随机分配到对照组 (CTR)、急性 (ACT) 或重复 (RPT) 可卡因给药组。在挑战日,每天服用可卡因 (15 mg/kg) 或生理盐水后,经过 10 天的冲洗和立体定向手术后,RPT 和 ACT 组接受可卡因,CTR 组接受生理盐水。在收集微量透析液的同时监测水平运动,以确定细胞外 GABA、谷氨酸和牛磺酸水平。血液样本中的激素测定证实了 OVX 的激素状态较低。攻击给药后,SHAM-RPT 雌性大鼠发生可卡因致敏。未致敏的 OVX-RPT 大鼠在可卡因给药后 30 分钟显示 GABA 峰值,谷氨酸和牛磺酸水平没有变化。因此,mPFC 中 GABA 水平升高和血清雌激素水平降低消除了去卵巢雌性大鼠的可卡因致敏行为。我们讨论了这些发现对女性荷尔蒙影响中可卡因敏化研究照明的未来模型的一些可能影响。

更新日期:2020-10-07
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