Differential orexin/hypocretin expression in addiction-prone and -resistant rats selectively bred for high (HiS) and low (LoS) saccharin intake.
Differential orexin/hypocretin expression in addiction-prone and -resistant rats selectively bred for high (HiS) and low (LoS) saccharin intake.
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DOI：
10.1016/j.neulet.2012.05.066
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发表时间：
2012-07-26
影响因子：
2.5
通讯作者：
Carroll ME
中科院分区：
文献类型：
--
作者：
Holtz NA;Zlebnik NE;Carroll ME
与低（LoS）糖精摄入量饲养的大鼠相比，选择性饲养高（HiS）糖精摄入量的大鼠在成瘾的几个阶段表现出更高的药物寻求行为。HiS大鼠也消耗大量的高可口的物质相比，LoS大鼠，然而，鲜为人知的是调节HiS和LoS线之间发现的不同行为的神经生物学底物。食欲素是一种神经肽，与药物滥用和可口物质过度消费的条件线索有关，HiS和LoS表型中的差异食欲素活性可能会增强我们对食物和药物奖励之间密切关系的理解，并最终导致食物和药物成瘾。外侧下丘脑（LH）和穹窿周围区（PFA）是与调节摄食行为和成瘾过程有关的脑区，含有广泛投射到整个大脑的食欲素能神经元。因此，我们调查食欲素和c-Fos的表达LH和PFA使用免疫组化HiS和LoS大鼠后，无论是控制或可卡因（15毫克/公斤）注射。结果表明，与LoS大鼠相比，在LH和PFA中，HiS大鼠具有更高的食欲素阳性细胞计数，无论可卡因（与盐水）治疗如何。与此相反，c-Fos表达所指示的神经元活动在HiS与LoS大鼠的这些脑区中没有差异。这些结果表明，食欲素系统可能参与了基因介导的强迫性，奖励驱动的行为的脆弱性的差异方面。
Rats that have been selectively bred for high (HiS) saccharin intake demonstrate elevated drug-seeking behavior in several phases of addiction compared to those bred for low (LoS) saccharin intake. HiS rats also consume greater amounts of highly palatable substances compared to LoS rats; however, little is known about the neurobiological substrates moderating the divergent behaviors found between the HiS and LoS lines. Orexins are neuropeptides that have been implicated in the conditioned cue aspects of drug abuse and overconsumption of palatable substances, and differential orexin activity in the HiS and LoS phenotypes may enhance our understanding of the close relationship between food and drug reward, and ultimately food and drug addiction. The lateral hypothalamus (LH) and perifornical area (PFA) are brain regions that have been implicated in regulating feeding behavior and addiction processes, and contain orexinergic neurons that project broadly throughout the brain. Thus, we investigated orexin and c-Fos expression in the LH and PFA using immunohistochemistry in HiS and LoS rats following either control or cocaine (15 mg/kg) injections. Results indicated that HiS rats have higher orexin-positive cell counts compared to LoS rats in both the LH and PFA, regardless of cocaine (vs. saline) treatment. In contrast, neuronal activity indicated by c-Fos expression did not differ in either of these brain areas in HiS vs. LoS rats. These results suggest that the orexin system may be involved in aspects of genetically mediated differences in vulnerability to compulsive, reward-driven behaviors.
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DOI：
10.1111/j.1460-9568.2009.06844.x
发表时间：
2009-08
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Smith RJ;See RE;Aston-Jones G
通讯作者：
Aston-Jones G
影响因子：
3.4
作者：
Shoblock, James R.;Welty, Natalie;Galici, Ruggero
通讯作者：
Galici, Ruggero
影响因子：
2.3
作者：
SINCLAIR, JD;KAMPOVPOLEVOY, A;LI, TK
通讯作者：
LI, TK
影响因子：
5.4
作者：
Yakovenko, Veronica;Speidel, Elizabeth R.;Dess, Nancy K.
通讯作者：
Dess, Nancy K.
影响因子：
3.6
作者：
Holtz, Nathan A.;Carroll, Marilyn E.
通讯作者：
Carroll, Marilyn E.