Arginine vasopressin gene expression changes within the nucleus accumbens during environment elicited cocaine-conditioned response in rats.

Arginine vasopressin gene expression changes within the nucleus accumbens during environment elicited cocaine-conditioned response in rats.
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DOI:
10.1016/j.neuropharm.2009.06.040
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发表时间:
2010-01
期刊:
影响因子:
4.7
通讯作者:
Maldonado-Vlaar CS
Maldonado-Vlaar CS
中科院分区:
医学2区
文献类型:
--
作者:
Rodríguez-Borrero E;Rivera-Escalera F;Candelas F;Montalvo J;Muñoz-Miranda WJ;Walker JR;Maldonado-Vlaar CS

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众所周知,伏核(NAC)基因表达的变化发生在可卡因依赖的发展过程中。然而,识别与可卡因条件作用有关的特定基因还有待进一步研究。在环境诱导的可卡因调节的不同阶段,我们对NAC进行了高通量的基因表达谱分析。老鼠被分配到两种不同的环境条件下。可卡因条件组:皮下注射可卡因10 mg/kg。在被放入活动室之前。对照组大鼠在暴露在环境中之前接受了生理盐水注射。两组都在家中的笼子里注射了生理盐水。条件反射训练为期10天。然后,只有在第12天(测试阶段),动物才重新暴露在以前配对的环境中。我们发现,精氨酸加压素(AVP)基因在实验对象的环境诱导可卡因条件作用的所有阶段都有不同的表达。为了进一步验证我们的分子结果,进行了生化和免疫定位实验。我们发现伏隔纤维中AVP的存在以及可卡因调节后AVP蛋白水平的变化。此外,在可卡因条件性刺激的不同阶段,我们还观察了伏隔微量注入V1a受体激动剂[pGlu4,Cyt6,Arg8]AVP 4-91.0 ng/0.5μL,或V1a拮抗剂(CH2)5[Tyr(Me)2]AVP,1.0 ng/0.5μL或溶剂溶液(0.9%生理盐水)的效果。在获得过程中阻断NAC内的V1a受体会中断条件性反应的表达,而激活则会导致这一反应的增加。我们的发现提出了AVP在可卡因成瘾中的新角色。
It is known that changes in gene expression within the nucleus accumbens (NAc) occur during cocaine dependence development. However, identification of specific genes involved in cocaine conditioning awaits further investigation. We conducted a high throughput gene expression profile analysis of the NAc, during different stages of the environment-elicited cocaine conditioning. Rats were assigned to two different environmental conditions. Cocaine conditioned group received a cocaine injection (10 mg/kg, i.p.) prior to being placed in the activity chambers. Control rats received saline injections before being exposed to their environment. Both groups received a saline injection in their home cage. Conditioning training lasted for 10 days. Animals were then re-exposed to their previously paired environments only on day 12 (test session). We found that the gene for arginine vasopressin (AVP) was differentially expressed on experimental subjects during all stages of environment-elicited cocaine conditioning. To further validate our molecular results, biochemical and immunolocalization experiments were conducted. We found the presence of AVP within accumbal fibers and changes in AVP protein levels following cocaine conditioning. Moreover, we tested the effects of accumbal microinfusions of either AVP receptor V1A agonist [pGlu4, Cyt6, Arg8] AVP 4-9 1.0 ng/0.5μl, or V1A antagonist (CH2) 5[Tyr (Me) 2] AVP, 1.0 ng/0.5μl or vehicle solution (0.9% saline solution) during different stages of the cocaine conditioning. Blockade of V1A receptors within the NAc during acquisition interrupted the expression of the conditioned response, while activation leads to an increase in this response. Our findings propose a new role for AVP in cocaine addiction.
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发表时间: 1988-01-01
期刊: LIFE SCIENCES
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