Cottone P, Sabino V, Steardo L, Zorrilla EP. Intermittent access to preferred food reduces the reinforcing efficacy of chow in rats. Am J Physiol Regul Integr Comp Physiol 295: R1066 -R1076, 2008. First published July 30, 2008 doi:10.1152/ajpregu.90309.2008.-Intermittent, extended access to preferred diets increases their intake. However, the effects of such access on the acceptance and reinforcing efficacy of otherwise satisfying alternatives is less known. To investigate the role of nonnutritional contributions to the hypophagia that follows removal of preferred food, male Wistar rats were fed a chow diet (Chow A/I), preferred to their regular chow (Chow), which was equally consumed under 1-choice conditions to an even more preferred chocolate-flavored, sucrose-rich diet (Preferred). Rats then learned to obtain Chow A/I pellets under a progressive ratio schedule of reinforcement and were assigned to two matched groups. Each week, one group (n ϭ 15) was diet-cycled, receiving Chow A/I for 5 days followed by the Preferred diet for 2 days. Controls received Chow A/I daily (n ϭ 14). Progressive ratio sessions were performed daily during the 5 days that all subjects received Chow A/I in the home cage. Across 5 wk, diet-cycled rats progressively ate less of the otherwise palatable Chow A/I diet. Hypophagia was not due to greater prior intake or weight gain, motor impairment, or facilitated satiation and was associated with changes in progressive ratio performance that suggested a reduced reinforcing efficacy of the Chow A/I diet in diet-cycled animals. By week 4, diet-cycled animals began to overeat the preferred diet, especially during the first 6 h of renewed access, resembling a deprivation effect. The results suggest that intermittent access to highly preferred food, as practiced by many restrained eaters, may progressively decrease the acceptability of less palatable foods, and may promote relapse to more rewarding alternatives. limited access; food intake; negative contrast; deprivation; palatability PROVIDING LIMITED, RATHER than continuous, access to rewards is a procedure used to model excessive behaviors. For example, intermittent, but extended, access to substances of abuse, such as ethanol (8, 19, 24, 29, 66), nicotine (35, 66), cocaine (1, 2, 5, 49, 62, 69, 95), heroin (3, 56), and methamphetamine (48) induces behavioral and molecular adaptations in rodents which resemble features of drug dependence in humans (54, 99), including increased drug self-administration. Drug addicts themselves often show cyclic patterns of uncontrolled use vs. abstinence, a profile also modeled by intermittent access animal models.Cycles of access to and deprivation from palatable foods also have been used to model the dysregulated food-directed behavior seen in some humans. Restrained eaters attempt to limit themselves to "safe" foods, typically less palatable than "forbidden" foods, to which they often return in bouts of overeating (37,46,50,86,98). Accordingly, it has been proposed that animals given intermittent access ...