CRF system recruitment mediates dark side of compulsive eating
- Pietro Cottonea,b,c,d,1,2,
- Valentina Sabinoa,b,c,d,1,
- Marisa Robertoa,c,d,
- Michal Bajoe,
- Lara Pockrosa,
- Jennifer B. Frihaufa,c,d,f,
- Eva M. Feketea,c,d,
- Luca Steardog,
- Kenner C. Riceh,
- Dimitri E. Grigoriadisi,
- Bruno Contid,e,
- George F. Kooba,c and
- Eric P. Zorrillaa,c,d,2
- aCommittee on the Neurobiology of Addictive Disorders,
- cPearson Center for Alcoholism and Addiction Research,
- dHarold L. Dorris Neurological Research Institute, and
- eDepartment of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, CA 92037;
- bLaboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118;
- fNeuroscience Graduate Program, University of California San Diego, La Jolla, CA 92093;
- gDepartment of Human Physiology and Pharmacology, University of Rome La Sapienza, 00185 Rome, Italy;
- hChemical Biology Research Branch, National Institute on Drug Abuse and National Institute on Alcohol and Alcoholism, Rockville, MD 20892; and
- iNeurocrine Biosciences Inc., San Diego, CA 92130
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↵1P.C. and V.S. contributed equally to this work.
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Edited by L. L. Iversen, University of Oxford, Oxford, United Kingdom, and approved September 25, 2009 (received for review August 5, 2009)
Abstract
Dieting to control body weight involves cycles of deprivation from palatable food that can promote compulsive eating. The present study shows that rats withdrawn from intermittent access to palatable food exhibit overeating of palatable food upon renewed access and an affective withdrawal-like state characterized by corticotropin-releasing factor-1 (CRF1) receptor antagonist-reversible behaviors, including hypophagia, motivational deficits to obtain less palatable food, and anxiogenic-like behavior. Withdrawal was accompanied by increased CRF expression and CRF1 electrophysiological responsiveness in the central nucleus of the amygdala. We propose that recruitment of anti-reward extrahypothalamic CRF-CRF1 systems during withdrawal from palatable food, analogous to abstinence from abused drugs, may promote compulsive selection of palatable food, undereating of healthier alternatives, and a negative emotional state when intake of palatable food is prevented.
Footnotes
- 2To whom correspondence may be addressed. E-mail: cottone{at}bu.edu or ezorrilla{at}scripps.edu
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Author contributions: P.C., V.S., M.R., M.B., L.S., K.C.R., D.E.G., B.C., G.F.K., and E.P.Z. designed research; P.C., V.S., M.R., M.B., L.P., J.B.F., and E.M.F. performed research; K.C.R. and D.E.G. contributed new reagents/analytic tools; P.C., V.S., M.R., M.B., J.B.F., and E.P.Z. analyzed data; and P.C., V.S., and E.P.Z. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
