title: Mu opioid receptor modulation in the nucleus accumbens lowers voluntary wheel running in rats bred for high running motivation.
abstract: The exact role of opioid receptor signaling in mediating voluntary wheel running is unclear. To provide additional understanding, female rats selectively bred for motivation of low (LVR) versus high voluntary running (HVR) behaviors were used. Aims of this study were 1) to identify intrinsic differences in nucleus accumbens (NAc) mRNA expression of opioid-related transcripts and 2) to determine if nightly wheel running is differently influenced by bilateral NAc injections of either the mu-opioid receptor agonist D-Ala2, NMe-Phe4, Glyo5-enkephalin (DAMGO) (0.25, 2.5 μg/side), or its antagonist, naltrexone (5, 10, 20 μg/side). In Experiment 1, intrinsic expression of Oprm1 and Pdyn mRNAs were higher in HVR compared to LVR. Thus, the data imply that line differences in opioidergic mRNA in the NAc could partially contribute to differences in wheel running behavior. In Experiment 2, a significant decrease in running distance was present in HVR rats treated with 2.5 μg DAMGO, or with 10 μg and 20 μg naltrexone between hours 0-1 of the dark cycle. Neither DAMGO nor naltrexone had a significant effect on running distance in LVR rats. Taken together, the data suggest that the high nightly voluntary running distance expressed by HVR rats is mediated by increased endogenous mu-opioid receptor signaling in the NAc, that is disturbed by either agonism or antagonism. In summary, our findings on NAc opioidergic mRNA expression and mu-opioid receptor modulations suggest HVR rats, compared to LVR rats, express higher running levels mediated by an increase in motivation driven, in part, by elevated NAc opioidergic signaling.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO, United States. Electronic address: gnrp86@mail.missouri.edu.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Ruegsegger
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO, United States.
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Toedebusch
authors.affiliation: Department of Psychological Sciences, University of Missouri, Columbia, MO, United States; Christopher Bond Life Sciences Center, University of Missouri, Columbia MO, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Will
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO, United States; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United States; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United States; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United States.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Booth
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D021461:Animals, Outbred Strains; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D009042:Motivation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012420:Running / Q000502:physiology* / Q000523:psychology; D013045:Species Specificity
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; D009292:Narcotic Antagonists; C485765:Oprm1 protein, rat; D011498:Protein Precursors; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; C033660:preproenkephalin
keywords: DAMGO; Mesolimbic; Nucleus accumbens; Physical activity; Selective breeding; mu opioid receptor