Effect of neurokinin-1 receptor antagonist on alcohol reward in juvenile mice

Abstract

Objective To examine the effect of NK1 receptor (NK1R) antagonist L-703, 606 on ethanol-induced conditioned place preference (CPP) and levels of NK1R protein in different brain regions in juvenile mice. Methods Four-week-old male C57BL/6 mice were divided into high anxiety group and low anxiety group according to the percentage of time spent in open arms of elevated plus maze(EPM). Then the mice in the two groups were divided into control group and experimental group according to random number table, which were high anxiety control group, high anxiety experimental group, low anxiety control group and low anxiety experimental group, with 11 in each group. L-703, 606 was injected intraperitoneally 40 minutes before CPP training in the high and low anxiety experimental group, while the control group received solvent treatment. After CPP test, the anxiety level of four groups of mice was detected by EPM again. The expression of NK1R protein in hippocampus, prefrontal lobe and amygdala of mice was detected by Western blot. Results Compared with the high anxiety control group, the CPP value of the high anxiety experimental group was lower, and the difference was statistically significant ((77.7±9.3)s vs (13.6±13.0)s, P=0.002). Compared with the low anxiety control group, the CPP value of the low anxiety experimental group was lower, and the difference was statistically significant ((113.2±10.3)s vs (28.0±9.6)s, P 0.05) . Compared with the high anxiety control group, the expression of NK1R increased in hippocampus, prefrontal lobe and amygdala of mice in high anxiety experimental group (all P<0.05). And the expression of NK1R in the above three brain regions had the same result between the low anxiety control group and the low anxiety experimental group (all P<0.05). Conclusions L-703, 606 can attenuate ethanol-induced CPP but has no effect on anxiety-like behaviors, suggesting the direct effect of NK1R in alcohol reward in juvenile mice. Key words: Neurokinin 1 receptor; Alcohol use disorder; Conditioned place preference; Anxiety; Mice