AI Article Synopsis
- The study explores how the NK1 receptor system is linked to the desire for sweet substances like sucrose, potentially contributing to the obesity crisis fueled by sugar intake.
- Using the NK1 receptor antagonist ezlopitant in animal models, researchers found that it reduced sucrose consumption more effectively than it did for ethanol, indicating its unique influence on sweet cravings.
- Findings suggest that the NK1 receptor could be key in understanding motivation behind both natural appetites and substance abuse, highlighting its potential as a target for obesity treatments linked to excessive sugar consumption.
Article 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], . 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931709 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012527 | PLOS |
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Article Synopsis
- The study explores how the NK1 receptor system is linked to the desire for sweet substances like sucrose, potentially contributing to the obesity crisis fueled by sugar intake.
- Using the NK1 receptor antagonist ezlopitant in animal models, researchers found that it reduced sucrose consumption more effectively than it did for ethanol, indicating its unique influence on sweet cravings.
- Findings suggest that the NK1 receptor could be key in understanding motivation behind both natural appetites and substance abuse, highlighting its potential as a target for obesity treatments linked to excessive sugar consumption.
Metabolism, pharmacokinetics, and excretion of a nonpeptidic substance P receptor antagonist, ezlopitant, in normal healthy male volunteers: characterization of polar metabolites by chemical derivatization with dansyl chloride.
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The excretion, biotransformation, and pharmacokinetics of ezlopitant [(2-benzhydryl-1-aza-bicyclo[2.2.2]oct-3-yl)-(5-isopropyl-2-methoxy-benzyl)-amine], a substance P receptor antagonist, were investigated in healthy male volunteers after oral administration of a single 200-mg (approximately 93 microCi/subject) dose of [(14)C]ezlopitant.
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