Charntikov S, Falco A M, Fink K, Dwoskin L P, Bevins R A
Department of Psychology, University of New Hampshire, 15 Academic Way, Durham, NH 03824, USA.
Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE 68588-0308, USA.
Neuropharmacology. 2017 Feb;113(Pt A):354-366. doi: 10.1016/j.neuropharm.2016.10.014. Epub 2016 Oct 17.
Nicotine is the primary addictive component of tobacco products and its complex stimulus effects are readily discriminated by human and non-human animals. Previous research with rodents directly investigating the nature of the nicotine stimulus has been limited to males. The current study began to address this significant gap in the literature by training female and male rats to discriminate 0.4 mg/kg nicotine from saline in the discriminated goal-tracking task. In this task, access to sucrose was intermittently available on nicotine session. On interspersed saline session, sucrose was not available. Both sexes acquired the discrimination as evidenced by increased head entries into sucrose receptacle (goal-tracking) evoked by nicotine; the nicotine generalization curves were also similar between females and males. The pharmacological profile of the nicotine stimulus was assessed using substitution and targeted combination tests with the following ligands: sazetidine-A, PHA-543613, PNU-120596, bupropion, nornicotine, and cytisine. For females and males, nornicotine fully substituted for the nicotine stimulus, whereas sazetidine-A, bupropion, and cytisine all evoked partial substitution. Female and male rats responded in a similar manner to interaction tests where a combination of 1 mg/kg of sazetidine-A plus nicotine or nornicotine shifted the nicotine dose-effect curve to the left. The combination of sazetidine-A plus bupropion or cytisine failed to do so. These findings begin to fill a significant gap the in scientific literature by studying the nature of the nicotine stimulus and response to therapeutically interesting combinations using a model that includes both sexes.
尼古丁是烟草制品中的主要成瘾成分，其复杂的刺激效应很容易被人类和非人类动物识别。以往对啮齿动物直接研究尼古丁刺激本质的研究仅限于雄性。当前的研究通过在辨别目标追踪任务中训练雌性和雄性大鼠区分0.4mg/kg尼古丁和生理盐水，开始填补文献中的这一重大空白。在这个任务中，在尼古丁给药时段蔗糖间歇性可得。在穿插的生理盐水给药时段，蔗糖不可得。两性都学会了这种辨别，表现为尼古丁诱发的进入蔗糖容器（目标追踪）的头部探入次数增加；雌性和雄性的尼古丁泛化曲线也相似。使用以下配体进行替代和靶向组合试验，评估尼古丁刺激的药理学特征：扎替丁-A、PHA-543613、PNU-120596、安非他酮、去甲烟碱和金雀花碱。对于雌性和雄性，去甲烟碱完全替代了尼古丁刺激，而扎替丁-A、安非他酮和金雀花碱都诱发了部分替代。雌性和雄性大鼠对相互作用试验的反应相似，在该试验中，1mg/kg扎替丁-A加尼古丁或去甲烟碱的组合使尼古丁剂量效应曲线向左移动。扎替丁-A加安非他酮或金雀花碱的组合未能做到这一点。这些发现通过使用包括两性的模型研究尼古丁刺激的本质以及对具有治疗意义的组合的反应，开始填补科学文献中的一个重大空白。
