title: Mu-opioid receptor inhibition decreases voluntary wheel running in a dopamine-dependent manner in rats bred for high voluntary running.
abstract: The mesolimbic dopamine and opioid systems are postulated to influence the central control of physical activity motivation. We utilized selectively bred rats for high (HVR) or low (LVR) voluntary running behavior to examine (1) inherent differences in mu-opioid receptor (Oprm1) expression and function in the nucleus accumbens (NAc), (2) if dopamine-related mRNAs, wheel-running, and food intake are differently influenced by intraperitoneal (i.p.) naltrexone injection in HVR and LVR rats, and (3) if dopamine is required for naltrexone-induced changes in running and feeding behavior in HVR rats. Oprm1 mRNA and protein expression were greater in the NAc of HVR rats, and application of the Oprm1 agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) to dissociated NAc neurons produced greater depolarizing responses in neurons from HVR versus LVR rats. Naltrexone injection dose-dependently decreased wheel running and food intake in HVR, but not LVR, rats. Naltrexone (20mg/kg) decreased tyrosine hydroxylase mRNA in the ventral tegmental area and Fos and Drd5 mRNA in NAc shell of HVR, but not LVR, rats. Additionally, lesion of dopaminergic neurons in the NAc with 6-hydroxydopamine (6-OHDA) ablated the decrease in running, but not food intake, in HVR rats following i.p. naltrexone administration. Collectively, these data suggest the higher levels of running observed in HVR rats, compared to LVR rats, are mediated, in part, by increased mesolimbic opioidergic signaling that requires downstream dopaminergic activity to influence voluntary running, but not food intake.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO, United States.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Ruegsegger
authors.affiliation: Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute at Lake Nona, Orlando, FL, United States.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Brown
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO, United States.
authors.forename: M Cathleen
authors.initials: MC
authors.lastname: Kovarik
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United States.
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Miller
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. Electronic address: boothf@missouri.edu.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Booth
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D007274:Injections, Intraperitoneal; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012420:Running / Q000502:physiology*; D057185:Sedentary Behavior; D013045:Species Specificity; D014836:Volition
chemical_list: D009292:Narcotic Antagonists; C485765:Oprm1 protein, rat; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D016627:Oxidopamine; D004298:Dopamine
keywords: mu opioid receptor; naltrexone; nucleus accumbens; physical activity; selective breeding