McLaughlin Jay P, Ganno Michelle L, Eans Shainnel O, Mizrachi Elisa, Paris Jason J
Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port Saint Lucie, FL 34987, USA.
Curr HIV Res. 2014;12(6):415-23. doi: 10.2174/1570162x1206150311160133.
Exposure to HIV-1 trans-activator of transcription (Tat) protein potentiates the psychostimulant effects of cocaine, but the functional consequences of the interaction between HIV-1 Tat and other abused drugs is poorly understood. We hypothesized that exposure to HIV-1 Tat would potentiate the rewarding effects of ethanol. GT-tg transgenic mice, where Tat protein is conditionally expressed in brain by a doxycycline-dependent GFAP-linked promoter, were used to test the effects of Tat on ethanol-conditioned place preference (CPP). Compared to uninduced littermates or doxycycline-treated C57BL/6J mice, Tat-induced GT-tg mice demonstrated a 3-fold increase in ethanol-CPP. The potentiation of ethanol-CPP was dependent on the dose and duration of doxycycline treatment used to express Tat protein. Moreover, induction of Tat protein after the extinction of CPP produced reinstatement without additional exposure to ethanol. Together, these data suggest that CNS exposure to HIV-1 Tat protein potentiates the rewarding effects of ethanol in mice.
暴露于HIV-1转录反式激活因子（Tat）蛋白会增强可卡因的精神刺激作用，但对于HIV-1 Tat与其他滥用药物之间相互作用的功能后果却知之甚少。我们推测，暴露于HIV-1 Tat会增强乙醇的奖赏效应。GT-tg转基因小鼠通过强力霉素依赖性胶质纤维酸性蛋白（GFAP）连接启动子在大脑中条件性表达Tat蛋白，用于测试Tat对乙醇条件性位置偏爱（CPP）的影响。与未诱导的同窝小鼠或强力霉素处理的C57BL/6J小鼠相比，Tat诱导的GT-tg小鼠的乙醇-CPP增加了3倍。乙醇-CPP的增强取决于用于表达Tat蛋白的强力霉素处理的剂量和持续时间。此外，在CPP消退后诱导Tat蛋白会产生复吸，而无需再次接触乙醇。这些数据共同表明，中枢神经系统暴露于HIV-1 Tat蛋白会增强小鼠对乙醇的奖赏效应。
