Pipkin Joseph A, Cruz Bryan, Flores Rodolfo J, Hinojosa Cecilia A, Carcoba Luis M, Ibarra Melissa, Francis Wendy, Nazarian Arbi, O'Dell Laura E
Department of Psychology, The University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79902, USA.
Department of Pharmaceutical Sciences, Western University of Health Sciences, 309 East Second Street, Pomona, CA, 91766, USA.
Psychopharmacology (Berl). 2017 May;234(9-10):1615-1622. doi: 10.1007/s00213-017-4592-y. Epub 2017 Mar 24.
It is presently unclear whether diabetic rats experience greater rewarding effects of nicotine and/or negative affective states produced by nicotine withdrawal.
The present study utilized a rodent model of diabetes to examine the rewarding effects of nicotine and negative affective states and physical signs produced by withdrawal.
Separate groups of rats received systemic administration of either vehicle or streptozotocin (STZ), which destroys insulin-producing beta cells in the pancreas and elevates glucose levels. Place conditioning procedures were utilized to compare the rewarding effects of nicotine (conditioned place preference; CPP) and negative affective states produced by withdrawal (conditioned place aversion; CPA) in vehicle- and STZ-treated rats. CPA and physical signs of withdrawal were compared after administration of the nicotinic receptor antagonist mecamylamine to precipitate withdrawal in nicotine-dependent rats. A subsequent study utilized elevated plus maze (EPM) procedures to compare anxiety-like behavior produced by nicotine withdrawal in vehicle- and STZ-treated rats.
STZ-treated rats displayed greater rewarding effects of nicotine and a larger magnitude of aversive effects and physical signs produced by withdrawal as compared to vehicle-treated controls. STZ-treated rats also displayed higher levels of anxiety-like behavior on the EPM during nicotine withdrawal as compared to controls.
The finding that both nicotine reward and withdrawal are enhanced in a rodent model of diabetes implies that the strong behavioral effects of nicotine promote tobacco use in persons with metabolic disorders, such as diabetes.
目前尚不清楚糖尿病大鼠是否会体验到尼古丁更大的奖赏效应和/或尼古丁戒断所产生的负面情绪状态。
本研究利用啮齿动物糖尿病模型来检验尼古丁的奖赏效应以及戒断所产生的负面情绪状态和身体体征。
将大鼠分为不同组，分别给予溶剂或链脲佐菌素（STZ）进行全身给药，STZ会破坏胰腺中产生胰岛素的β细胞并提高血糖水平。采用位置条件反射程序来比较在给予溶剂和STZ的大鼠中尼古丁的奖赏效应（条件性位置偏爱；CPP）以及戒断所产生的负面情绪状态（条件性位置厌恶；CPA）。在给予烟碱受体拮抗剂美加明以使尼古丁依赖大鼠出现戒断反应后，比较CPA和戒断的身体体征。随后的一项研究采用高架十字迷宫（EPM）程序来比较给予溶剂和STZ的大鼠在尼古丁戒断时产生的焦虑样行为。
与给予溶剂的对照组相比，给予STZ的大鼠表现出更大的尼古丁奖赏效应以及更大程度的戒断厌恶效应和身体体征。与对照组相比，给予STZ的大鼠在尼古丁戒断期间在EPM上也表现出更高水平的焦虑样行为。
在糖尿病啮齿动物模型中尼古丁奖赏和戒断均增强这一发现表明，尼古丁强烈的行为效应会促使患有代谢紊乱（如糖尿病）的人使用烟草。
