title: Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice.
abstract: Physical exercise can improve cognition but whether this is related to motivation levels is unknown. Voluntary wheel running is a rewarding activity proposed as a model of motivation to exercise. To question the potential effects of exercise motivation on subsequent behaviour, we used a pharmacological approach targeting some reward mechanisms. The stress hormone corticosterone has rewarding effects mediated by activation of low affinity glucocorticoid receptors (GR). To investigate whether corticosterone synthesis motivates exercise via activation of GRs and subsequently, impacts on behaviour, we treated C57BL/6J mice acutely with the inhibitor of corticosterone synthesis metyrapone (35mg/kg) or repeatedly with the GR antagonist mifepristone (30mg/kg) prior to 1-h running wheel sessions. To investigate whether reducing motivation to exercise impacts on behaviour, we antagonised running-induced dopamine D2/D3 receptors activation with sulpiride (25 or 50mg/kg) and assessed locomotor, anxiety-related and memory performance after 20 running sessions over 4 weeks. We found that corticosterone synthesis contributes to running levels, but the maintenance of running behaviour was not mediated by activation of GRs. Intermittent exercise was not associated with changes in behavioural or cognitive performance. The persistent reduction in exercise levels triggered by sulpiride also had limited impact on behavioural performance, although the level of performance for some behaviours was related to the level of exercise. Altogether, these findings indicate that corticosterone and dopamine D2/D3 receptor activation contribute to the motivation for wheel running, but suggest that motivation for exercise is not a sufficient factor to alter behaviour in healthy mice.
authors.affiliation: University of Nottingham Medical School, School of Life Sciences, Neuroscience Group, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
authors.forename: Mohamed Elsaed
authors.initials: ME
authors.lastname: Ebada
authors.affiliation: University of Nottingham Medical School, School of Life Sciences, Neuroscience Group, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Kendall
authors.affiliation: University of Nottingham Medical School, School of Life Sciences, Neuroscience Group, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom. Electronic address: marie.pardon@nottingham.ac.uk.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Pardon
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008797:Metyrapone / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D018697:Nootropic Agents / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D012420:Running / Q000502:physiology* / Q000523:psychology*; D013469:Sulpiride / Q000494:pharmacology; D014836:Volition / Q000187:drug effects / Q000502:physiology
chemical_list: C000600618:DRD2 protein, mouse; D018492:Dopamine Antagonists; C493594:Drd3 protein, mouse; D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D018697:Nootropic Agents; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D013469:Sulpiride; D003345:Corticosterone; D008797:Metyrapone
keywords: C57BL/6J mice; Corticosterone; Dopamine D2/D3 receptors; Glucocorticoid receptors; Memory; Voluntary wheel running