title: Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats.
abstract: Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel "junk-food" diet on the development of obesity and metabolic dysfunction, 2) over-consumption of "junk-food" in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, "junk-food" diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals.
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Vollbrecht
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Cameron W
authors.initials: CW
authors.lastname: Nobile
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Chadderdon
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Jutkiewicz
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA. Electronic address: ferrario@umich.edu.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Ferrario
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000502:physiology; D004032:Diet; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005247:Feeding Behavior / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D007328:Insulin / Q000097:blood; D008297:Male; D009042:Motivation / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009765:Obesity / Q000503:physiopathology* / Q000523:psychology*; D017207:Rats, Sprague-Dawley
chemical_list: D018765:Dopamine Uptake Inhibitors; D007328:Insulin; D003042:Cocaine
keywords: Cocaine; Feeding; Junk-food; Nucleus accumbens; Obesity; Reward; Striatum