Effects of ceftriaxone on ethanol intake: a possible role for xCT and GLT-1 isoforms modulation of glutamate levels in P rats.
Effects of ceftriaxone on ethanol intake: a possible role for xCT and GLT-1 isoforms modulation of glutamate levels in P rats.
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DOI：
10.1007/s00213-014-3545-y
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发表时间：
2014-10
影响因子：
3.4
通讯作者：
Sari, Youssef
中科院分区：
文献类型：
--
作者：
Alhaddad, Hasan;Das, Sujan C.;Sari, Youssef
有证据表明，谷氨酸转运蛋白1（GLT-1）和胱氨酸/谷氨酸交换转运蛋白（xCT）在维持谷氨酸稳态中至关重要。我们最近证明，头孢曲松治疗可诱导GLT 1水平上调并减少乙醇摄入量;然而，关于xCT对乙醇摄入量的影响知之甚少。在这项研究中，我们研究了头孢曲松对连续和复发样乙醇饮用中xCT水平的影响，以及GLT-1亚型和复发样乙醇摄入中谷氨酸天冬氨酸转运蛋白（GLAST）的影响。P组大鼠自由选择15%和30%乙醇和水5周，然后剥夺乙醇2周。将大鼠用头孢曲松（100 mg/kg，i. p.）或生理盐水。剥夺期结束后，将P大鼠再次暴露于自由选择的15%和30%乙醇和水，连续9天。第二组P大鼠连续给予乙醇5周，然后给予头孢曲松（100 mg/kg，i. p.）或生理盐水6周。头孢曲松显著减弱复发样乙醇摄入。重要的是，头孢曲松的这种作用部分与前额叶皮层（PFC）和丘脑核（NAc）中GLT-1a和GLT-1b亚型和xCT水平的上调相关。各组间GLAST表达无显着差异。我们还发现，头孢曲松治疗增加xCT水平在PFC和NAc连续乙醇摄入。这些发现表明，xCT和GLT-1亚型可能是治疗酒精依赖的靶蛋白。
Evidence suggests that glutamate transporter 1 (GLT-1) and cystine/glutamate exchanger transporter (xCT) are critical in maintaining glutamate homeostasis. We have recently demonstrated that ceftriaxone treatment induced up-regulation of GLT1 levels and attenuated ethanol intake; however, less is known about the involvement of xCT on ethanol intake. In this study, we investigated the effects of ceftriaxone on the levels of xCT in both continuous and relapse-like ethanol drinking, as well as GLT-1 isoforms, and glutamate aspartate transporter (GLAST) in relapse-like ethanol intake. P rats received free choice of 15 and 30 % ethanol and water for 5 weeks and then deprived of ethanol for 2 weeks. Rats were treated with ceftriaxone (100 mg/kg, i.p.) or saline during the last 5 days of the 2-week deprivation period. After deprivation period, P rats were re-exposed to free choice of 15 and 30 % ethanol and water for nine consecutive days. A second group of P rats was given continuous ethanol access for 5 weeks, then ceftriaxone (100 mg/kg, i.p.) or saline throughout the week 6. Ceftriaxone significantly attenuated relapse-like ethanol intake. Importantly, this effect of ceftriaxone was associated in part with upregulation of the levels of GLT-1a and GLT-1b isoforms and xCT in the prefrontal cortex (PFC) and the nucleus accumbens (NAc). There were no significant differences in GLAST expression among all groups. We also found that ceftriaxone treatment increased xCT levels in both PFC and NAc in continuous ethanol intake. These findings suggest that xCT and GLT-1 isoforms might be target proteins for the treatment of alcohol dependence.
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DOI：
10.1097/00000374-200108000-00008
发表时间：
2001-08-01
影响因子：
3.2
作者：
Rodd-Henricks, ZA;Bell, RL;Li, TK
通讯作者：
Li, TK
影响因子：
10.6
作者：
Besheer, Joyce;Grondin, Julie J. M.;Cannady, Reginald;Sharko, Amanda C.;Faccidomo, Sara;Hodge, Clyde W.
通讯作者：
Hodge, Clyde W.
影响因子：
3.3
作者：
Sari, Y.;Sreemantula, S. N.
通讯作者：
Sreemantula, S. N.
影响因子：
5.3
作者：
Chen, WZ;Mahadomrongkul, V;Rosenberg, PA
通讯作者：
Rosenberg, PA
影响因子：
5.3
作者：
Mitani, A;Tanaka, K
通讯作者：
Tanaka, K