Mu-opioid receptor inhibition decreases voluntary wheel running in a dopamine-dependent manner in rats bred for high voluntary running.

Ruegsegger GN, Brown JD, Kovarik MC, Miller DK, Booth FW
Neuroscience. 2016 339: 525-537

PMID: 27743985 · DOI:10.1016/j.neuroscience.2016.10.020

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.

Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

MeSH Terms (21)

Animals Cells, Cultured Dopamine Enkephalin, Ala(2)-MePhe(4)-Gly(5)- Feeding Behavior Female Injections, Intraperitoneal Motivation Motor Activity Naltrexone Narcotic Antagonists Neurons Nucleus Accumbens Oxidopamine Rats Receptors, Opioid, mu RNA, Messenger Running Sedentary Behavior Species Specificity Volition

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