1. ¹Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA
2. ²Harold L. Dorris Neurological Research Institute, The Scripps Research Institute, La Jolla, CA, USA
3. ³Department of Human Physiology and Pharmacology, University of Rome La Sapienza, Rome, Italy

Correspondence: Dr P Cottone or Dr EP Zorrilla, Committee on the Neurobiology of Addictive Disorders, SP30-2400, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. Tel: +1 858 784 7464 (PC) or +1 858 784 7416 (EPZ), Fax: +1 858 784 7405; E-mail: cottone@scripps.edu (PC) or ezorrilla@scripps.edu (EPZ)

⁴These authors equally contributed to this work.

Received 12 January 2007; Revised 2 March 2007; Accepted 20 March 2007; Published online 18 April 2007.

Abstract

Binge eating and an increased role for palatability in determining food intake are abnormal adaptations in feeding behavior linked to eating disorders and body weight dysregulation. The present study tested the hypothesis that rats with limited access to highly preferred food would develop analogous opioid-dependent learned adaptations in feeding behavior, with associated changes in metabolism and anxiety-like behavior. For this purpose, adolescent female Wistar rats were daily food deprived (2 h) and then offered 10-min access to a feeder containing chow followed sequentially by 10-min access to a different feeder containing either chow (chow/chow; n=7) or a highly preferred, but macronutrient-comparable, sucrose-rich diet (chow/preferred; n=8). Chow/preferred-fed rats developed binge-like hyperphagia of preferred diet from the second feeder and anticipatory chow hypophagia from the first feeder with a time course suggesting associative learning. The feeding adaptations were dissociable in onset, across individuals, and in their dose–response to the opioid-receptor antagonist nalmefene, suggesting that they represent distinct palatability-motivated processes. Chow/preferred-fed rats showed increased anxiety-like behavior in relation to their propensity to binge as well as increased feed efficiency, body weight, and visceral adiposity. Chow/preferred-fed rats also had increased circulating leptin levels and decreased growth hormone and 'active' ghrelin levels. Thus, the short-term control of food intake in rats with restricted access to highly preferred foods comes to rely more on hedonic, rather than nutritional, properties of food, through associative learning mechanisms. Such rats show changes in ingestive, metabolic, endocrine, and anxiety-related measures, which resemble features of binge eating disorders or obesity.