Enhanced nicotine self-administration and suppressed dopaminergic systems in a rat model of diabetes
Enhanced nicotine self-administration and suppressed dopaminergic systems in a rat model of diabetes
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DOI：
10.1111/adb.12074
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发表时间：
2014-11-01
影响因子：
3.4
通讯作者：
Nazarian, Arbi
中科院分区：
文献类型：
--
作者：
O'Dell, Laura E.;Natividad, Luis A.;Nazarian, Arbi
糖尿病患者吸烟的倾向较高；然而，尚不清楚他们是否会感受到尼古丁的增强奖励作用。因此，这项研究检查了尼古丁在糖尿病啮齿动物模型中的增强作用，该模型涉及使用链脲佐菌素（STZ），链脲佐菌素是一种对胰腺胰岛素产生细胞有毒的药物。第一项研究比较了 STZ 和媒介物治疗的大鼠，这些大鼠在 23 小时内接受静脉自我给药（IVSA）尼古丁或盐水，并同时获得食物和水。为了检查多巴胺对我们行为影响的贡献，在尼古丁或盐水 IVSA 10 天后，比较了伏隔核 (NAc) 中的多巴胺转运蛋白 (DAT)、D1 和 D2 受体水平。还比较了尼古丁给药后 NAc 中的多巴胺水平。最后，评估了尼古丁代谢和尼古丁 IVSA 的剂量依赖性效应。结果显示，与对照组相比，STZ 治疗的大鼠尼古丁摄入量增加，食物和水摄入量显着增加。蛋白质分析显示，与媒介物处理的大鼠相比，STZ 处理的大鼠 NAc 中 DAT 增加，D1 受体水平降低，无论 IVSA 状况如何。 STZ 治疗的大鼠在基线期间和对尼古丁的反应中也表现出 NAc 多巴胺水平受到抑制。 STZ 治疗并没有改变我们对尼古丁代谢的评估。此外，STZ 治疗以剂量依赖性方式增加尼古丁 IVSA。我们的研究结果表明，STZ 治疗增加了尼古丁的奖励作用。这表明尼古丁的强烈强化作用可能导致糖尿病患者更多地使用烟草。
Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared in the nucleus accumbens (NAc) following 10 days of nicotine or saline IVSA. Dopamine levels in the NAc were also compared following nicotine administration. Lastly, nicotine metabolism and dose-dependent effects of nicotine IVSA were assessed. The results revealed that STZ-treated rats displayed enhanced nicotine intake and a robust increase in food and water intake relative to controls. Protein analysis revealed an increase in DAT and a decrease in D1 receptor levels in the NAc of STZ-versus vehicle-treated rats regardless of IVSA condition. STZ-treated rats also displayed suppressed NAc dopamine levels during baseline and in response to nicotine. STZ treatment did not alter our assessment of nicotine metabolism. Furthermore, STZ treatment increased nicotine IVSA in a dose-dependent manner. Our findings suggest that STZ-treatment increased the rewarding effects of nicotine. This suggests that strong reinforcing effects of nicotine may contribute to greater tobacco use in patients with diabetes.