title: Leptin signaling in the medial nucleus tractus solitarius reduces food seeking and willingness to work for food.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kanoski
authors.affiliation: Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Alhadeff
authors.affiliation: Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Fortin
authors.affiliation: Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Gilbert
authors.affiliation: Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Grill
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects / Q000523:psychology*; D005502:Food; D005508:Food Deprivation; D005518:Food Preferences / Q000187:drug effects / Q000523:psychology; D007839:Functional Laterality / Q000187:drug effects; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D020738:Leptin; D013395:Sucrose