Assessment of nicotine withdrawal-induced changes in sucrose preference in mice

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 14 days 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 Subsequently, our results demonstrated a time-dependent and dose-related reduction in sucrose preference in nicotine withdrawn male C57BL/6J mice, indicative of a decrease in responding for positive affective stimuli.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We also found the reduction for positive affective stimuli and time spent in the light side was not present in nicotine withdrawn beta 2 and alpha 6 KO mice, suggesting that these nicotinic subunits are involved in the affective signs of nicotine withdrawal.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.