Orexin A mediation of time spent moving in rats: Neural mechanisms
The brain regulates energy balance and spontaneous physical activity, including both small- and large-motor activities. Neural mediators of spontaneous physical activity are currently undefined, although the amount of time spent in sedentary positions versus standing and ambulating may be important...
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Published in | Neuroscience Vol. 142; no. 1; pp. 29 - 36 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
29.09.2006
Elsevier |
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Abstract | The brain regulates energy balance and spontaneous physical activity, including both small- and large-motor activities. Neural mediators of spontaneous physical activity are currently undefined, although the amount of time spent in sedentary positions versus standing and ambulating may be important in the energetics of human obesity. Orexin A, a neuropeptide produced in caudal hypothalamic areas and projecting throughout the neuraxis, enhances arousal and spontaneous physical activity. To test the hypothesis that orexin A affects the amount of time spent moving, we injected orexin A (0–1000 pmol) into three orexin projection sites in male Sprague–Dawley rats: hypothalamic paraventricular nucleus, rostral lateral hypothalamic area and substantia nigra pars compacta, and measured spontaneous physical activity. Orexin A affects local GABA release and we co-injected orexin A with a GABA agonist, muscimol, in each brain site. Dopamine signaling is important to substantia nigra function and so we also co-injected a dopamine 1 receptor antagonist (SCH 23390) in the substantia nigra pars compacta. In all brain sites orexin A significantly increased time spent vertical and ambulating. Muscimol significantly and dose-dependently inhibited orexin A effects on time spent moving only when administered to the rostral lateral hypothalamic area. In the substantia nigra pars compacta, SCH 23390 completely blocked orexin A–induced ambulation. These data indicate that orexin A influences time spent moving, in three brain sites utilizing separate signaling mechanisms. That orexin A modulation of spontaneous physical activity occurs in brain areas with multiple roles indicates generalization across brain site, and may reflect a fundamental mechanism for enhancing activity levels. This potential for conferring physical activity stimulation may be useful for inducing shifts in time spent moving, which has important implications for obesity. |
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AbstractList | The brain regulates energy balance and spontaneous physical activity, including both small- and large-motor activities. Neural mediators of spontaneous physical activity are currently undefined, although the amount of time spent in sedentary positions versus standing and ambulating may be important in the energetics of human obesity. Orexin A, a neuropeptide produced in caudal hypothalamic areas and projecting throughout the neuraxis, enhances arousal and spontaneous physical activity. To test the hypothesis that orexin A affects the amount of time spent moving, we injected orexin A (0–1000 pmol) into three orexin projection sites in male Sprague–Dawley rats: hypothalamic paraventricular nucleus, rostral lateral hypothalamic area and substantia nigra pars compacta, and measured spontaneous physical activity. Orexin A affects local GABA release and we co-injected orexin A with a GABA agonist, muscimol, in each brain site. Dopamine signaling is important to substantia nigra function and so we also co-injected a dopamine 1 receptor antagonist (SCH 23390) in the substantia nigra pars compacta. In all brain sites orexin A significantly increased time spent vertical and ambulating. Muscimol significantly and dose-dependently inhibited orexin A effects on time spent moving only when administered to the rostral lateral hypothalamic area. In the substantia nigra pars compacta, SCH 23390 completely blocked orexin A–induced ambulation. These data indicate that orexin A influences time spent moving, in three brain sites utilizing separate signaling mechanisms. That orexin A modulation of spontaneous physical activity occurs in brain areas with multiple roles indicates generalization across brain site, and may reflect a fundamental mechanism for enhancing activity levels. This potential for conferring physical activity stimulation may be useful for inducing shifts in time spent moving, which has important implications for obesity. |
Author | Kotz, C.M. Thorpe, A.J. Wang, C. Novak, C.M. Levine, J.A. Kiwaki, K. Teske, J.A. |
Author_xml | – sequence: 1 givenname: C.M. surname: Kotz fullname: Kotz, C.M. email: kotzx004@umn.edu organization: Veterans Affairs Medical Center, Geriatric Research, Education and Clinical Care (11G), One Veterans Drive, Minneapolis, MN 55417, USA – sequence: 2 givenname: C. surname: Wang fullname: Wang, C. organization: Veterans Affairs Medical Center, Geriatric Research, Education and Clinical Care (11G), One Veterans Drive, Minneapolis, MN 55417, USA – sequence: 3 givenname: J.A. surname: Teske fullname: Teske, J.A. organization: Department of Food Science and Nutrition, University of Minnesota, 1334 Eckles Avenue, St. Paul, MN 55108, USA – sequence: 4 givenname: A.J. surname: Thorpe fullname: Thorpe, A.J. organization: Graduate Program in Neuroscience, University of Minnesota, 420 Delaware Street, St. Paul, MN 55455, USA – sequence: 5 givenname: C.M. surname: Novak fullname: Novak, C.M. organization: Endocrine Research Unit, Mayo Clinic Rochester, 200 First Street Southwest, Rochester, MN 55905, USA – sequence: 6 givenname: K. surname: Kiwaki fullname: Kiwaki, K. organization: Endocrine Research Unit, Mayo Clinic Rochester, 200 First Street Southwest, Rochester, MN 55905, USA – sequence: 7 givenname: J.A. surname: Levine fullname: Levine, J.A. organization: Minnesota Obesity Center, Geriatric Research, Education and Clinical Care (11G), One Veterans Drive, Minneapolis, MN 55417, USA |
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Keywords | substantia nigra pc substantia nigra lateral hypothalamus rLHa PVN OX2R hypothalamic paraventricular nucleus NEAT OX1R hypocretin aCSF locomotor activity orexin Rat Rodentia Central nervous system Lateral hypothalamus Paraventricular nucleus Neuropeptide Encephalon Locomotion Vertebrata Mammalia Locus niger Animal Orexin |
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SubjectTerms | Analysis of Variance Animals Behavior, Animal - drug effects Behavior, Animal - physiology Benzazepines - pharmacology Biological and medical sciences Dopamine Antagonists - pharmacology Dose-Response Relationship, Drug Drug Interactions Fundamental and applied biological sciences. Psychology GABA Agonists - pharmacology hypocretin Hypothalamic Area, Lateral - drug effects hypothalamic paraventricular nucleus Intracellular Signaling Peptides and Proteins - pharmacology lateral hypothalamus locomotor activity Male Movement - drug effects Muscimol - pharmacology Neuropeptides - pharmacology orexin Orexins Paraventricular Hypothalamic Nucleus - drug effects Rats Rats, Sprague-Dawley substantia nigra Substantia Nigra - drug effects Time Factors Vertebrates: nervous system and sense organs |
Title | Orexin A mediation of time spent moving in rats: Neural mechanisms |
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