Intra-ventral tegmental area HIV-1 Tat1-86 attenuates nicotine-mediated locomotor sensitization and alters mesocorticolimbic ERK and CREB signaling in rats.
Intra-ventral tegmental area HIV-1 Tat1-86 attenuates nicotine-mediated locomotor sensitization and alters mesocorticolimbic ERK and CREB signaling in rats.
复制标题
DOI：
10.3389/fmicb.2015.00540
复制
发表时间：
2015
影响因子：
5.2
通讯作者：
Harrod SB
中科院分区：
文献类型：
--
作者：
Zhu J;Midde NM;Gomez AM;Sun WL;Harrod SB
HIV阳性者的吸烟流行率远远高于HIV阴性者。我们已经证明，HIV-1转基因大鼠表现出尼古丁介导的运动活性减弱，中皮质边缘区cAMP反应元件结合蛋白(CREB)和细胞外调节蛋白(ERK1/2)信号发生改变。本研究探讨了HIV-1反式转录激活因子(TAT)蛋白在HIV-1转基因大鼠尼古丁介导的行为和信号通路改变中的作用。大鼠双侧微量注射重组TAT1-86(25μg/侧)或向腹侧被盖区注射载体，然后进行运动测试，每天静脉注射尼古丁(0.05 mg/kg，游离碱，1次/d)或生理盐水。此外，我们还检测了CREB(PCREB)和ERK1/2(pERK1/2)在前额叶皮质(PFC)、伏隔核(NAC)和VTA中的磷酸化水平。TAT降低了生理盐水对照组大鼠的基线活性，并减弱了尼古丁诱导的行为敏化。在反复注射生理盐水后，与TAT组相比，赋形剂对照组在NAc和VTA的pERK1和pERK2的基础水平都较低。反复尼古丁注射后，赋形剂组NAc和VTA的PERK1和VTA的PERK2均增加，而TAT组无明显变化。此外，重复尼古丁注射降低了TAT组PFC和VTA中的pCREB，但在赋形剂组中没有。因此，这些发现表明，在VTA直接注射TAT可能介导了CREB和ERK的活动，以响应尼古丁诱导的运动活动。
Cigarette smoking prevalence in the HIV-positive individuals is profoundly higher than that in the HIV-negative individuals. We have demonstrated that HIV-1 transgenic rats exhibit attenuated nicotine-mediated locomotor activity, altered cAMP response element binding protein (CREB) and extracellular regulated kinase (ERK1/2) signaling in the mesocorticolimbic regions. This study investigated the role of HIV-1 transactivator of transcription (Tat) protein in the alterations of nicotine-mediated behavior and the signaling pathway observed in the HIV-1 transgenic rats. Rats received bilateral microinjection of recombinant Tat1–86 (25 μg/side) or vehicle directed at ventral tegmental area (VTA) followed by locomotor testing in response to 13 daily intravenous injections of nicotine (0.05 mg/kg, freebase, once/day) or saline. Further, we examined the phosphorylated levels of CREB (pCREB) and ERK1/2 (pERK1/2) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and VTA. Tat diminished baseline activity in saline control rats, and attenuated nicotine-induced behavioral sensitization. Following repeated saline injection, the basal levels of pERK1 in the NAc and VTA and pERK2 in VTA were lower in the vehicle control group, relative to the Tat group. After repeated nicotine injection, pERK1 in NAc and VTA and pERK2 in VTA were increased in the vehicle group, but not in the Tat group. Moreover, repeated nicotine injections decreased pCREB in the PFC and VTA in the Tat group but not in the vehicle group. Thus, these findings indicate that the direct injection of Tat at the VTA may mediate CREB and ERK activity in response to nicotine-induced locomotor activity.
登录
查看更多内容
影响因子：
3.7
作者：
Cao J;Wang S;Wang J;Cui W;Nesil T;Vigorito M;Chang SL;Li MD
通讯作者：
Li MD
影响因子：
3.4
作者：
Ferrari, R;Le Novère, N;Zoli, M
通讯作者：
Zoli, M
影响因子：
7.3
作者：
CLARKE, PBS;KUMAR, R
通讯作者：
KUMAR, R
HIV-1 蛋白治疗大鼠的多巴胺能亢进和可卡因致敏。
影响因子：
4.7
作者：
Ferris MJ;Frederick-Duus D;Fadel J;Mactutus CF;Booze RM
通讯作者：
Booze RM
伏隔核Creb活性对于尼古丁条件的位置偏好是必需的。
DOI：
10.1038/npp.2009.11
发表时间：
2009-07
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--