Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
Pharmacol Biochem Behav. 2017 Oct;161:47-52. doi: 10.1016/j.pbb.2017.08.013. Epub 2017 Sep 15.
Anhedonia, induced by nicotine withdrawal, may serve as an important affective sign that reinforces tobacco use and smoking relapse rates in humans. Animal models provide a way to investigate the underlying neurobiological factors involved in the decrease in responding for positive affective stimuli during nicotine withdrawal and may aid in drug development for nicotine dependence. Thus, we explored the use of the sucrose preference test to measure nicotine withdrawal-induced reduction in response for positive affective stimuli in mice. C57BL/6J and knockout (KO) mice were chronically exposed to different doses of nicotine through surgically implanted subcutaneous osmotic minipumps for 14days and underwent spontaneous nicotine withdrawal on day 15. A sucrose preference time course was performed and the results were compared to another well-established affective sign of nicotine withdrawal, the reduction in time spent in light side, using the Light Dark Box test. Subsequently, our results demonstrated a time-dependent and dose-related reduction in sucrose preference in nicotine withdrawn male C57BL/6J mice, indicative of a decrease in responding for positive affective stimuli. Furthermore, the sucrose preference reduction during nicotine withdrawal was consistent with decrease in time spent in the light side of the Light Dark Box test. We also found the reduction for positive affective stimuli and time spent in the light side was not present in nicotine withdrawn β2 and α6 KO mice, suggesting that these nicotinic subunits are involved in the affective signs of nicotine withdrawal. Thus, this report highlights the potential utility of the sucrose preference test as a useful measure of the decrease in responding for positive affective stimuli during spontaneous nicotine withdrawal.
快感缺失，由尼古丁戒断引起，可能是一种重要的情感标志，它加强了人类对烟草的使用和复吸率。动物模型为研究尼古丁戒断期间对正性情感刺激反应减少所涉及的潜在神经生物学因素提供了一种方法，并可能有助于尼古丁依赖的药物开发。因此，我们探索了使用蔗糖偏好测试来测量尼古丁戒断诱导的小鼠对正性情感刺激反应的减少。C57BL/6J 和敲除（KO）小鼠通过手术植入的皮下渗透微型泵接受不同剂量的尼古丁慢性暴露 14 天，并在第 15 天进行自发性尼古丁戒断。进行了蔗糖偏好时间过程，并将结果与另一种已确立的尼古丁戒断的情感标志，即光侧时间减少，使用明暗箱测试进行比较。随后，我们的结果表明，尼古丁戒断的雄性 C57BL/6J 小鼠的蔗糖偏好呈时间依赖性和剂量依赖性降低，表明对正性情感刺激的反应减少。此外，在尼古丁戒断期间，蔗糖偏好的降低与明暗箱测试中光侧时间的减少一致。我们还发现，在尼古丁戒断的β2 和α6 KO 小鼠中，没有正性情感刺激的减少和光侧时间的减少，这表明这些烟碱受体亚基参与了尼古丁戒断的情感标志。因此，本报告强调了蔗糖偏好测试作为测量自发性尼古丁戒断期间对正性情感刺激反应减少的有用方法的潜力。
