Department of Pharmaceutical Sciences, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA.
Department of Psychology, University of Texas at El Paso, 500 W. University Avenue, El Paso, TX, 79968, USA.
Neurosci Lett. 2020 Mar 16;721:134825. doi: 10.1016/j.neulet.2020.134825. Epub 2020 Feb 6.
Morbidity and mortality attributed to type 2 diabetes have exponentially increased in the US. At exceptionally high risk is a subpopulation of persons with type 2 diabetes who smoke, which are shown to have decreased success rates of smoking cessation than euglycemic smokers. Preclinical research in our laboratory has shown that the rewarding effects of nicotine are enhanced in the streptozotocin and high-fat diet rodent model of diabetes. It is presently unclear whether this enhancement of nicotine reward can be demonstrated in other insulin resistant rat models. This study aimed to determine if a similar increase in nicotine reward is found in Goto-Kakizaki (GK) rats, a model of the spontaneous formation of insulin resistance in an inbred sub-strain of Wistar rat. Nicotine conditioned place preference (CPP) was examined in Sprague-Dawley (SD), Wistar, and GK rats. A robust nicotine CPP was found in SD and Wistar rats, but nicotine CPP was not detected in GK rats. Locomotor activity was also evaluated in all three strains, and GK rats demonstrated significantly less activity as compared to SD and Wistar rats. To further assess reward behavior in GK rats, consumption of saccharin solution was measured over a 48 -h period. GK rats showed a significant increase in saccharin intake compared to SD rats. These findings suggest that GK rats experience an enhanced hedonic processing as compared to SD rats. The lack of nicotine CPP in GK rats may be due to deficits in learning and memory, thus hindering their ability to acquire or express a place preference.
在美国，2 型糖尿病导致的发病率和死亡率呈指数级增长。有一个 2 型糖尿病亚人群的风险极高，他们吸烟，与血糖正常的吸烟者相比，戒烟成功率明显降低。我们实验室的临床前研究表明，链脲佐菌素和高脂肪饮食诱导的糖尿病啮齿动物模型中，尼古丁的奖赏作用增强。目前尚不清楚这种尼古丁奖赏的增强是否可以在其他胰岛素抵抗大鼠模型中表现出来。本研究旨在确定在自发性胰岛素抵抗形成的近交 Wistar 大鼠亚系 Goto-Kakizaki（GK）大鼠中是否发现类似的尼古丁奖赏增加。在 Sprague-Dawley（SD）、Wistar 和 GK 大鼠中检查了尼古丁条件性位置偏好（CPP）。在 SD 和 Wistar 大鼠中发现了强大的尼古丁 CPP，但在 GK 大鼠中未检测到尼古丁 CPP。还评估了所有三种品系的运动活动，与 SD 和 Wistar 大鼠相比，GK 大鼠的活动明显减少。为了进一步评估 GK 大鼠的奖励行为，测量了 48 小时内蔗糖溶液的消耗量。与 SD 大鼠相比，GK 大鼠的蔗糖摄入量明显增加。这些发现表明，与 SD 大鼠相比，GK 大鼠的享乐加工增强。GK 大鼠中缺乏尼古丁 CPP 可能是由于学习和记忆缺陷，从而阻碍了它们获得或表达位置偏好的能力。
