Leptin Signaling in the Medial Nucleus Tractus Solitarius Reduces Food Seeking and Willingness to Work for Food

Sep 5, 2013Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Leptin signals in a brain area controlling internal organs reduce food seeking and effort to get food

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Abstract

Unilateral leptin administration to the mNTS at a dose of 0.3 μg significantly suppressed food intake and motivated feeding behavior.

Leptin signaling in the mNTS reduces food intake by amplifying satiation signals from the gastrointestinal tract.
The suppression of appetitive behavior, as measured by operant lever pressing for sucrose, occurred regardless of the animal's energy status.
Food-seeking behavior, assessed through conditioned place preference, was only reduced in rats that were chronically food-restricted.
Leptin signaling did not affect the motivation for opioid rewards, indicating a selective influence on food-related behavior.
These findings suggest a novel role for leptin receptor signaling in regulating food motivation that varies with energy availability.

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The adipose-derived hormone leptin signals in the medial nucleus tractus solitarius (mNTS) to suppress food intake, in part, by amplifying within-meal gastrointestinal (GI) satiation signals. Here we show that mNTS leptin receptor (LepRb) signaling also reduces appetitive and motivational aspects of feeding, and that these effects can depend on energy status. Using the lowest dose that significantly suppressed 3-h cumulative food intake, unilateral leptin (0.3 μg) administration to the mNTS (3 h before testing) reduced operant lever pressing for sucrose under increasing work demands (progressive ratio reinforcement schedule) regardless of whether animals were energy deplete (food restricted) or replete (ad libitum fed). However, in a separate test of food-motivated responding in which there was no opportunity to consume food (conditioned place preference (CPP) for an environment previously associated with a palatable food reward), mNTS leptin administration suppressed food-seeking behavior only in chronically food-restricted rats. On the other hand, mNTS LepRb signaling did not reduce CPP expression for morphine reinforcement regardless of energy status, suggesting that mNTS leptin signaling differentially influences motivated responding for food vs opioid reward. Overall results show that mNTS LepRb signaling reduces food intake and appetitive food-motivated responding independent of energy status in situations involving orosensory and postingestive contact with food, whereas food-seeking behavior independent of food consumption is only reduced by mNTS LepRb activation in a state of energy deficit. These findings reveal a novel appetitive role for LepRb signaling in the mNTS, a brain region traditionally linked with processing of meal-related GI satiation signals.

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Leptin Signaling in the Medial Nucleus Tractus Solitarius Reduces Food Seeking and Willingness to Work for Food

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