Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
PLoS One. 2013 Jul 24;8(7):e69453. doi: 10.1371/journal.pone.0069453. Print 2013.
Studies using mice and rats have demonstrated that nicotine induces a conditioned place preference (CPP), with more effective results obtained by using biased procedures. Zebrafish have also been used as a model system to identify factors influencing nicotine-associated reward by using an unbiased design. Here, we report that zebrafish exhibited putative nicotine biased CPP to an initially aversive compartment (nicotine-paired group). A counterbalanced nicotine-exposed control group did not show a significant preference shift, providing evidence that the preference shift in the nicotine-paired group was not due to a reduction of aversion for this compartment. Zebrafish preference was corroborated by behavioral analysis of several indicators of drug preference, such as time spent in the drug-paired side, number of entries to the drug-paired side, and distance traveled. These results provided strong evidence that zebrafish may actually develop a preference for nicotine, although the drug was administrated in an aversive place for the fish, which was further supported by molecular studies. Reverse transcription-quantitative real-time PCR analysis depicted a significant increase in the expression of α7 and α6 but not α4 and β2 subunits of the nicotinic receptor in nicotine-paired zebrafish brains. In contrast, zebrafish brains from the counterbalanced nicotine group showed no significant changes. Moreover, CREB phosphorylation, an indicator of neural activity, accompanied the acquisition of nicotine-CPP. Our studies offered an incremental value to the drug addiction field, because they further describe behavioral features of CPP to nicotine in zebrafish. The results suggested that zebrafish exposed to nicotine in an unfriendly environment can develop a preference for that initially aversive place, which is likely due to the rewarding effect of nicotine. Therefore, this model can be used to screen exogenous and endogenous molecules involved in nicotine-associated reward in vertebrates.
使用老鼠和老鼠的研究表明，尼古丁诱导条件性位置偏好（CPP），通过使用有偏见的程序获得更有效的结果。斑马鱼也被用作模型系统，通过使用无偏设计来识别影响尼古丁相关奖励的因素。在这里，我们报告说，斑马鱼表现出对最初令人厌恶的隔间（尼古丁配对组）的假定尼古丁偏见 CPP。平衡的尼古丁暴露对照组没有表现出明显的偏好转移，这提供了证据表明，配对组的偏好转移不是由于对该隔间的厌恶感降低。斑马鱼的偏好通过药物偏好的几个指标的行为分析得到证实，例如在药物配对侧花费的时间，进入药物配对侧的次数和行驶的距离。这些结果提供了强有力的证据，表明斑马鱼实际上可能对尼古丁产生偏好，尽管药物在鱼类的厌恶场所中给予，但通过分子研究进一步得到支持。反转录定量实时 PCR 分析显示，在尼古丁配对的斑马鱼大脑中，烟碱受体的 α7 和 α6 亚基但不是 α4 和 β2 亚基的表达显著增加。相比之下，来自平衡的尼古丁组的斑马鱼大脑没有显示出显着变化。此外，CREB 磷酸化，神经活动的一个指标，伴随着尼古丁-CPP 的获得。我们的研究为药物成瘾领域提供了增量价值，因为它们进一步描述了斑马鱼中尼古丁 CPP 的行为特征。结果表明，在不友好环境中暴露于尼古丁的斑马鱼可以对最初令人厌恶的地方产生偏好，这可能是由于尼古丁的奖赏作用。因此，该模型可用于筛选涉及脊椎动物中尼古丁相关奖励的外源性和内源性分子。
