Selective breeding for high alcohol preference increases the sensitivity of the posterior VTA to the reinforcing effects of nicotine.
Selective breeding for high alcohol preference increases the sensitivity of the posterior VTA to the reinforcing effects of nicotine.
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DOI：
10.1111/adb.12048
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发表时间：
2014-09
影响因子：
3.4
通讯作者：
Rodd ZA
中科院分区：
文献类型：
--
作者：
Hauser SR;Bracken AL;Deehan GA Jr;Toalston JE;Ding ZM;Truitt WA;Bell RL;McBride WJ;Rodd ZA
酒精和尼古丁的共同依赖率非常高。大量研究表明，酒精中毒和尼古丁依赖之间存在共同的遗传联系。目前的实验研究了大鼠高酒精偏好的选择性繁殖是否与后腹侧被盖区(PVTA)对尼古丁增强特性的敏感性增加有关。此外，尼古丁可以直接与5-羟色胺-3(5-HT3)受体结合，这已被证明在pVTA中介导了其他滥用药物的强化特性。Wistar大鼠被分配到允许在两级(活动和非活动)操作室中自我注入0、10、50、100、200、400或800μM尼古丁的组。P组大鼠自体注入0、1、10、50或100μM尼古丁。还观察了5-HT3受体拮抗剂与尼古丁在pVTA内的协同作用。在Wistar大鼠中，P大鼠自我注射的尼古丁浓度低于支持自我给药所需的浓度。此外，与Wistar大鼠相比，P大鼠接受了更多的50和100μM尼古丁的自我注射。包括一种5HT3受体拮抗剂(LY-278,584，或扎可必利)，与尼古丁减少主动杠杆上的反应。总体而言，数据支持高酒精偏好的选择性育种与pVTA对尼古丁增强特性的敏感性增加之间的联系。此外，数据表明，可能需要激活5HT3受体来维持pVTA内尼古丁的局部增强作用。
The rate of co-dependency for alcohol and nicotine is extremely high. Numerous studies have indicated that there is a common genetic association for alcoholism and nicotine dependency. The current experiments examined whether selective breeding for high alcohol preference in rats may be associated with increased sensitivity of the posterior ventral tegmental area (pVTA) to the reinforcing properties of nicotine. In addition, nicotine can directly bind to the serotonin-3 (5-HT3) receptor, which has been shown to mediate the reinforcing properties of other drugs of abuse within the pVTA Wistar rats were assigned to groups that were allowed to self-infuse 0, 10, 50, 100, 200, 400 or 800 μM nicotine in 2-lever (active and inactive) operant chambers. P rats were allowed to self-infuse 0, 1, 10, 50 or 100 μM nicotine. Co-infusion of 5-HT3 receptor antagonists with nicotine into the pVTA was also determined. P rats self-infused nicotine at lower concentrations than required to support self-administration in Wistar rats. In addition, P rats received more self-infusions of 50 and 100 μM nicotine than Wistar rats. Including a 5HT3 receptor antagonist (LY-278,584, or zacopride) with nicotine reduced responding on the active lever. Overall, the data support an association between selective breeding for high alcohol preference and increased sensitivity of the pVTA to the reinforcing properties of nicotine. In addition, the data suggest that activation of 5HT3 receptors may be required to maintain the local reinforcing actions of nicotine within the pVTA.
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