Graduate Program in Health Sciences: Pharmacology and Toxicology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), 90050-170, Porto Alegre, RS, Brazil.
Graduate Program in Health Sciences: Pharmacology and Toxicology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), 90050-170, Porto Alegre, RS, Brazil; Pharmacy Program, Centro Universitário Metodista - IPA, Brazil; Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul (UFRGS), 90040-060, Porto Alegre, RS, Brazil.
Brain Res. 2020 Dec 15;1749:147144. doi: 10.1016/j.brainres.2020.147144. Epub 2020 Oct 7.
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.
动物模型表明，可卡因敏化是成瘾的行为标志物，在完整性腺的雌性大鼠中比雄性大鼠更为明显，而卵巢切除术会抑制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递质变化。在这里，我们研究了可卡因挑战给药后，完整性腺或卵巢切除的雌性大鼠内侧前额皮质（mPFC）中 GABA、谷氨酸和牛磺酸水平的体内变化。成年雌性大鼠被双侧卵巢切除术（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，经过八天的每日可卡因（15mg/kg）或生理盐水给药和十天的洗脱和立体定向手术，RPT 和 ACT 组接受可卡因，而 CTR 组接受生理盐水。同时监测水平运动以收集微透析液，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 的激素水平较低。SHAM-RPT 雌性大鼠在挑战给药后发生可卡因敏化。未敏化的 OVX-RPT 大鼠在可卡因给药后 30 分钟表现出 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会消除卵巢切除雌性大鼠的可卡因敏化行为。我们讨论了这些发现对未来女性激素影响的可卡因敏化研究模型的一些可能意义。
