, Volume 177, Issue 3, pp 324–335 | Cite as

Leptin and post-prandial satiety: acute central leptin more potently reduces meal frequency than meal size in the rat

  • Eric P. ZorrillaEmail author
  • Koki Inoue
  • Glenn R. Valdez
  • Antoine Tabarin
  • George F. Koob
Original Investigation



Many attempts to understand ingestion have sought to clarify the control of meals. Little is known about the effects of the anorexogenic hormone leptin on meal patterning.


The present study sought to perform a dose–response analysis of the effects of acute central leptin administration on meal patterning using a validated, objective meal definition and to compare these results to those obtained with a previously used, subjective meal definition.


To validate the objective meal definition pharmacologically, the microstructural effects of the well-studied compound fenfluramine (SC 0, 1, 2, 4 mg/kg) on spontaneous nocturnal intake were determined in mature, non-deprived male Wistar rats (n=8) using a full Latin square design. The effects of intracerebroventricular leptin administration (0, 0.3, 1, 3, 6.25 μg; n=10) were also examined, and perceived meal patterns obtained from the objective and subjective definitions were compared.


Fenfluramine reduced meal size and eating rate at doses that did not reduce meal frequency or duration. In contrast, comparably anorectic doses of leptin had potent post-meal satiety-like effects, reducing meal frequency and prolonging the intermeal interval without reducing average meal size, a finding opposite to that suggested by the previously used subjective meal definition. Unlike comparably and more anorectic doses of fenfluramine, leptin non-specifically reduced both prandial and non-prandial drinking.


Acute increases in central leptin levels may potently augment post-prandial satiety and influence body-fluid homeostasis. The results reveal unappreciated central modes of action for the ob protein which qualitatively differ from the intra-meal satiating-like effects of fenfluramine.


Food intake Water intake Obesity Satiation Appetite suppressant Anorectic drugs Food-associated drinking Serotonin Post-meal interval Meal pattern analysis 



This study was supported by DK26741 and DK64871 from the National Institute of Diabetes and Digestive and Kidney Diseases (E.P.Z., G.F.K.). A.T. was supported by grants from the Fondation pour la Recherche Médicale and the Action Thématique Concertée “Nutrition” from INSERM. G.R.V. was supported by AA05563, an Individual National Research Service Award from the National Institute on Alcohol Abuse and Alcoholism. The authors thank Robert Lintz, Carmen Carrillo and Lindsay Reinhardt for technical contributions, and Mike Arends for editorial assistance. This is publication number 16298-NP from The Scripps Research Institute. The experiments comply with the current laws of the United States of America.


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Eric P. Zorrilla
    • 1
    Email author
  • Koki Inoue
    • 1
    • 2
  • Glenn R. Valdez
    • 1
  • Antoine Tabarin
    • 1
    • 3
  • George F. Koob
    • 1
  1. 1.Department of NeuropharmacologyThe Scripps Research InstituteLa JollaUSA
  2. 2.Department of NeuropsychiatryOsaka City University Medical SchoolOsakaJapan
  3. 3.Department of EndocrinologyUniversity of Bordeaux 2BordeauxFrance

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