title: Endogenous nociceptin modulates diet preference independent of motivation and reward.
abstract: Previous studies show that the opioid peptide nociceptin stimulates food intake. Here, we studied nociceptin receptor knockout (NOP KO) mice in various behavioral paradigms designed to differentiate psychological and physiological loci at which endogenous nociceptin might control feeding. When presented a choice under food restriction, NOP KO mice displayed reduced preference for high sucrose diet, but lower intake of high fat diet under no-choice conditions. These responses were absent under ad libitum feeding conditions. Conditioned place preference to high fat diet under food-deprived conditions was unaltered in NOP KO mice, suggesting no difference in reward responses. Furthermore, operant food self-administration under a variety of conditions showed no genotype-dependent differences, suggesting no differences in the motivational properties of food. Taste reactivity to sucrose was unchanged in NOP KO mice, though NOP KO mice had altered aversive reactions to quinine solutions under ad libitum feeding, suggesting minor differences in the affective impact of palatable and unpalatable tastants. Although NOP KO mice re-fed following food-deprivation showed normal increases in plasma glucose and insulin, multidimensional scaling analysis showed that the relationship between these measures, body weight and plasma leptin was substantially disrupted in NOP KO, particularly in fasted mice. Additionally, the typical positive relationship between body weight and plasma leptin was considerably weaker in NOP KO mice. Together, these findings suggest that endogenous nociceptin differentially modulates diet preference depending on macronutrient content and homeostatic state, independently of the motivating, rewarding or orosensory properties of food, but may involve metabolic or postingestive processes.
authors.affiliation: Molecular Neuropathology Group, RIKEN Brain Science Institute, Wakoshi, Saitama 351-0198, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Koizumi
authors.forename: Barbara
authors.initials: B
authors.lastname: Cagniard
authors.forename: Niall P
authors.initials: NP
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D003216:Conditioning, Operant; D004041:Dietary Fats; D019422:Dietary Sucrose; D004327:Drinking Behavior / Q000502:physiology; D005260:Female; D005508:Food Deprivation; D005518:Food Preferences / Q000502:physiology* / Q000523:psychology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009042:Motivation; D018847:Opioid Peptides / Q000235:genetics / Q000502:physiology*; D011957:Receptors, Opioid / Q000235:genetics; D012201:Reward; D055697:Taste Perception / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D019422:Dietary Sucrose; D007328:Insulin; D020738:Leptin; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722287:Oprl1 protein, mouse