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Effects of repeated cocaine exposure and withdrawal on voluntary ethanol drinking, and the expression of glial glutamate transporters in mesocorticolimbic system of P rats.
Molecular and Cellular Neuroscience ( IF 3.5 ) Pub Date : 2017-04-27 , DOI: 10.1016/j.mcn.2017.04.008
Alaa M Hammad 1 , Yusuf S Althobaiti 1 , Sujan C Das 1 , Youssef Sari 1
Affiliation  

Glutamatergic neurotransmission within the brain's reward circuits plays a major role in the reinforcing properties of both ethanol and cocaine. Glutamate homeostasis is regulated by several glutamate transporters, including glutamate transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate aspartate transporter (GLAST). Cocaine exposure has been shown to induce a dysregulation in glutamate homeostasis and a decrease in the expression of GLT-1 and xCT in the nucleus accumbens (NAc). In this study, alcohol preferring (P) rats were exposed to free-choice of ethanol (15% and 30%) and/or water for five weeks. On Week 6, rats were administered (i.p.) cocaine (10 and 20mg/kg) or saline for 12 consecutive days. This study tested two groups of rats: the first group was euthanized after seven days of repeated cocaine i.p. injection, and the second group was deprived from cocaine for five days and euthanized at Day 5 after cocaine withdrawal. Only repeated cocaine (20mg/kg, i.p.) exposure decreased ethanol intake from Day 3 through Day 8. Co-exposure of cocaine and ethanol decreased the relative mRNA expression and the expression of GLT-1 in the NAc but not in the medial prefrontal cortex (mPFC). Importantly, co-exposure of cocaine and ethanol decreased relative expression of xCT in the NAc but not in the mPFC. Our findings demonstrated that chronic cocaine exposure affects ethanol intake; and ethanol and cocaine co-abuse alters the expression of glial glutamate transporters.

中文翻译:

可卡因反复暴露和戒断对自愿饮酒的影响以及P大鼠中皮质糖皮质系统中神经胶质谷氨酸转运蛋白的表达。

大脑奖励回路中的谷氨酸能神经传递在增强乙醇和可卡因的特性中起着重要作用。谷氨酸稳态由几种谷氨酸转运蛋白调节,包括1型谷氨酸转运蛋白(GLT-1),胱氨酸/谷氨酸转运蛋白(xCT)和谷氨酸天冬氨酸转运蛋白(GLAST)。可卡因暴露已被证明可引起伏谷核(NAc)中谷氨酸稳态的失调和GLT-1和xCT表达的降低。在这项研究中,偏爱酒精(P)的大鼠暴露于自由选择的乙醇(15%和30%)和/或水中五个星期。在第6周,连续12天给予(ip)大鼠可卡因(10和20mg / kg)或生理盐水。这项研究测试了两组大鼠:第一组在重复注射可卡因7天后被安乐死 注射,第二组被剥夺可卡因5天,并在撤出可卡因后第5天安乐死。从第3天到第8天,仅重复可卡因(20mg / kg,ip)暴露会减少乙醇摄入,同时暴露于可卡因和乙醇会降低NAc中相对mRNA表达和GLT-1的表达,但不会降低额前内侧皮质的表达。 (mPFC)。重要的是,可卡因和乙醇的共同暴露降低了NAc中xCT的相对表达,但没有降低mPFC中的xCT相对表达。我们的发现表明,长期接触可卡因会影响乙醇的摄入。乙醇和可卡因共同滥用会改变神经胶质谷氨酸转运蛋白的表达。)暴露会降低第3天到第8天的乙醇摄入量。同时暴露于可卡因和乙醇会降低NAc中的相对mRNA表达和GLT-1的表达,但不会降低内侧前额叶皮层(mPFC)的表达。重要的是,可卡因和乙醇的共同暴露降低了NAc中xCT的相对表达,但没有降低mPFC中的xCT相对表达。我们的发现表明,长期接触可卡因会影响乙醇的摄入。乙醇和可卡因共同滥用会改变神经胶质谷氨酸转运蛋白的表达。)暴露会降低第3天到第8天的乙醇摄入量。同时暴露于可卡因和乙醇会降低NAc中的相对mRNA表达和GLT-1的表达,但不会降低内侧前额叶皮层(mPFC)的表达。重要的是,可卡因和乙醇的共同暴露降低了NAc中xCT的相对表达,但没有降低mPFC中的xCT相对表达。我们的发现表明,长期接触可卡因会影响乙醇的摄入。乙醇和可卡因共同滥用会改变神经胶质谷氨酸转运蛋白的表达。我们的发现表明,长期接触可卡因会影响乙醇的摄入。乙醇和可卡因共同滥用会改变神经胶质谷氨酸转运蛋白的表达。我们的发现表明,长期接触可卡因会影响乙醇的摄入。乙醇和可卡因共同滥用会改变神经胶质谷氨酸转运蛋白的表达。
更新日期:2019-11-01
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