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风味无关的维持、消除和恢复小鼠的脂肪自我给药。

Flavor-independent maintenance, extinction, and reinstatement of fat self-administration in mice.

机构信息

John B. Pierce Laboratory, New Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

出版信息

Biol Psychiatry. 2013 May 1;73(9):851-9. doi: 10.1016/j.biopsych.2013.02.028.

Abstract

BACKGROUND

Mounting evidence suggests that overeating may be conceptualized within the same behavioral and neurobiological framework as drug addiction. One potentially important difference between overeating versus drug abuse refers to the sensory stimulation of oral receptors by palatable foods, a feature that may be required for reinforcement during intake. Likewise, postingestive effects and caloric content of food also contribute to reinforcing behavior and might influence the development of compulsive eating behavior. The purpose of the current study was to establish whether intragastric self-administration of fat emulsions, that is, bypassing the oral cavity, recapitulates some of the behavioral and neurobiological hallmarks of psychostimulant self-administration.

METHODS

We used behavioral assays in mice to assess acquisition, maintenance, extinction, and reinstatement of intragastric self-administration of lipid emulsions to determine the extent to which postoral fat self-administration recapitulates psychostimulant self-administration. Striatal dopamine efflux during behavioral tasks was determined by brain microdialysis coupled to chromatographic-electrochemical analyses.

RESULTS

We show that in direct analogy to drug self-administration, 1) decreases in fat dose concentration were met with compensatory increases in response rates aimed at maintaining constant hourly caloric intake; 2) rates of responding markedly increased during both extinction and progressive ratio schedules of reinforcement; and 3) elevations in striatal dopamine levels observed during maintenance were markedly attenuated during extinction sessions, only to be restored on reinstatement.

CONCLUSIONS

Our data thus support the contention that stimulation of oral receptors by caloric foods may not be required for the expression of certain addiction-related neurobehavioral markers.

摘要

背景

越来越多的证据表明,暴饮暴食可能与药物成瘾一样,属于同一行为和神经生物学框架。暴饮暴食与滥用药物之间的一个潜在重要区别在于,美味食物对口腔感受器的感官刺激,这一特征可能是摄入过程中强化的必要条件。同样,食物的餐后效应和热量含量也有助于强化行为,并可能影响强迫性进食行为的发展。本研究的目的是确定胃内脂肪乳剂的自我给药是否重现了一些精神兴奋剂自我给药的行为和神经生物学特征。

方法

我们使用小鼠的行为测定来评估脂质乳剂的胃内自我给药的获得、维持、消退和再激发,以确定口服后脂肪自我给药在多大程度上重现了精神兴奋剂自我给药。通过与色谱-电化学分析相结合的脑微透析来测定行为任务期间纹状体多巴胺的流出。

结果

我们发现,与药物自我给药直接类似,1)降低脂肪剂量浓度会导致反应率的补偿性增加,以维持恒定的每小时热量摄入;2)在消退和递增比率强化方案期间,反应率显著增加;3)在维持期间观察到的纹状体多巴胺水平升高在消退期间明显减弱,仅在再激发时恢复。

结论

因此,我们的数据支持这样一种观点,即热量食物对口腔感受器的刺激可能不是表达某些与成瘾相关的神经行为标记所必需的。

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