Increased expression of 5-HT1B receptors in rat nucleus accumbens via virally mediated gene transfer increases voluntary alcohol consumption
Increased expression of 5-HT1B receptors in rat nucleus accumbens via virally mediated gene transfer increases voluntary alcohol consumption
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DOI：
10.1016/j.alcohol.2006.04.003
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发表时间：
2006-02-01
期刊：
影响因子：
2.3
通讯作者：
Neumaier, J. F.
中科院分区：
文献类型：
--
作者：
Hoplight, B. J.;Sandygren, N. A.;Neumaier, J. F.
血清素5-HT 1B受体与人类的酒精中毒和啮齿动物的酒精消耗有关。我们推测这些位于延髓核投射神经元轴突末梢的受体调节酒精奖赏机制。为了验证这一假设，我们测量了酒精消耗的大鼠接受双边微量注射的病毒载体产生5-HT 1B过表达（HA 1B/GFP）。其他组接受对照（仅GFP）单纯疱疹病毒载体进入内侧NAcc壳或简单处理而不进行手术。所有动物单独饲养，手术前后在其饲养笼中连续获得水、6%乙醇和12%乙醇，体重增加的量或速率、进食量或总液体消耗量均无差异。手术前两组间的乙醇消耗量也没有差异。然而，手术后，HA 1B/GFP组消耗的乙醇是其他组的两倍。总乙醇消耗量的主要影响是显著的（p <0.05）;对照组之间没有差异。尽管在6%乙醇消耗量方面没有组间差异，但与两个对照组以及它们自己的术前摄入量相比，表达HA 1B/GFP的动物消耗的12%乙醇量大幅增加（p <0.05）。我们假设，增加5-HT 1B的表达在NAcc导致更大的奖励或减少12%乙醇的厌恶作用，从而导致自愿乙醇消费量增加。(c)2006年爱思唯尔公司All rights reserved.
Serotonin 5-HT1B receptors have been linked to alcoholism in humans and alcohol consumption in rodents. We hypothesize that these receptors, which are located on the axon terminals of nucleus accumbens' (NAcc) projection neurons, modulate alcohol reward mechanisms. To test this hypothesis, we measured ethanol consumption by rats that received bilateral microinjections of a viral vector producing 5-HT1B overexpression (HA1B/GFP). Other groups received either control (GFP-only) herpes simplex viral vectors into the medial NAcc shell or were handled briefly with no surgery. All animals were housed singly and had continuous access to water, 6% ethanol, and 12% ethanol in their home cages both before and after surgery.There were no differences in the amount or rate of weight gain, amount of food eaten, or total fluid consumed. There were also no differences in the amount of ethanol consumed between groups prior to surgery. However, after surgery, the HA1B/GFP group consumed twice as much ethanol as the other groups. The main effect of total ethanol consumption was significant (p < .05); the control groups did not differ from each other. Whereas there were no between-group differences in 6% ethanol consumption, there was a large increase in the amount of 12% ethanol consumed by the HA1B/GFP-expressing animals compared to the two control groups as well as to their own presurgery intake (p < .05). We hypothesize that increased 5-HT1B expression in NAcc led to either greater reward or reduced aversive effects from the 12% ethanol, thereby leading to increased voluntary ethanol consumption. (c) 2006 Elsevier Inc. All rights reserved.