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

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

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



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.


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.


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.


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.

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