title: Mu-opioid receptor knockout mice show diminished food-anticipatory activity.
abstract: We have previously suggested that during or prior to activation of anticipatory behaviour to a coming reward, mu-opioid receptors are activated. To test this hypothesis schedule induced food-anticipatory activity in mu-opioid receptor knockout mice was measured using running wheels. We hypothesized that mu-knockout mice show little food-anticipatory activity. In wildtype mice we observed that food-anticipatory activity increased proportional to reduced food intake levels during daily scheduled food access, and thus reflects the animal's physiological need for food. mu-Knockout mice do not adjust their schedule induced running wheel behaviour prior to and during feeding time in the same way as wildtype mice; rather than showing more running wheel activity before than during feeding, they showed an equal amount of activity before and during feeding. As food-anticipatory activity is dependent on the mesolimbic dopamine system and mu-opioid receptors regulate dopaminergic activity, these data suggest a change in the dopamine system's activity in mu-knockout mice. As we observed that mu-knockout mice tended to show a stronger locomotor activity response than wildtype mice to the indirect dopamine agonist d-amphetamine, it appears that the dopaminergic system per se is intact and sensitive to activation. We found no differences in the expression of pro-opiomelanocortin, a precursor of endogenous endorphin, in the arcuate nucleus between mu-knockout mice and wildtype mice during restricted feeding, showing that the mu-opioid receptor does not regulate endogenous endorphin levels. These data overall suggest a role for mu-opioid receptors in adapting reward related behaviour to the requirements of the environment.
authors.affiliation: Ethology and Animal Welfare, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 17, NL-3584 CL Utrecht, The Netherlands.
authors.forename: Martien J H
authors.initials: MJ
authors.lastname: Kas
authors.forename: Ruud
authors.initials: R
authors.lastname: van den Bos
authors.forename: Annemarie M
authors.initials: AM
authors.lastname: Baars
authors.forename: Marianne
authors.initials: M
authors.lastname: Lubbers
authors.forename: Heidi M B
authors.initials: HM
authors.lastname: Lesscher
authors.forename: Jacquelien J G
authors.initials: JJ
authors.lastname: Hillebrand
authors.forename: Alwin G
authors.initials: AG
authors.lastname: Schuller
authors.forename: John E
authors.initials: JE
authors.lastname: Pintar
authors.forename: Berry M
authors.initials: BM
authors.lastname: Spruijt
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000235:genetics; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005502:Food; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000172:deficiency / Q000502:physiology*; D012055:Reinforcement Schedule; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D017450:Receptors, Opioid, mu; D011333:Pro-Opiomelanocortin; D000661:Amphetamine