The neurokinin 1 receptor antagonist, ezlopitant, reduces appetitive responding for sucrose and ethanol

Abstract

Abstract
Background: The current obesity epidemic is thought to be partly driven by over-consumption of sugar-sweetened diets
and soft drinks. Loss-of-control over eating and addiction to drugs of abuse share overlapping brain mechanisms including
changes in motivational drive, such that stimuli that are often no longer ‘liked’ are still intensely ‘wanted’ [7,8]. The
neurokinin 1 (NK1) receptor system has been implicated in both learned appetitive behaviors and addiction to alcohol and
opioids; however, its role in natural reward seeking remains unknown.
Methodology/Principal Findings: We sought to determine whether the NK1-receptor system plays a role in the reinforcing
properties of sucrose using a novel selective and clinically safe NK1-receptor antagonist, ezlopitant (CJ-11,974), in three
animal models of sucrose consumption and seeking. Furthermore, we compared the effect of ezlopitant on ethanol
consumption and seeking in rodents. The NK1-receptor antagonist, ezlopitant decreased appetitive responding for sucrose
more potently than for ethanol using an operant self-administration protocol without affecting general locomotor activity.
To further evaluate the selectivity of the NK1-receptor antagonist in decreasing consumption of sweetened solutions, we
compared the effects of ezlopitant on water, saccharin-, and sodium chloride (NaCl) solution consumption. Ezlopitant
decreased intake of saccharin but had no effect on water or salty solution consumption.
Conclusions/Significance: The present study indicates that the NK1-receptor may be a part of a common pathway
regulating the self-administration, motivational and reinforcing aspects of sweetened solutions, regardless of caloric value,
and those of substances of abuse. Additionally, these results indicate that the NK1-receptor system may serve as a
therapeutic target for obesity induced by over-consumption of natural reinforcers.