Orexin A mediation of time spent moving in rats: Neural mechanisms

• Published in: Neuroscience Vol. 142; no. 1; pp. 29 - 36
• Main Authors: Kotz, C.M., Wang, C., Teske, J.A., Thorpe, A.J., Novak, C.M., Kiwaki, K., Levine, J.A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 29.09.2006; Elsevier
• Subjects: 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; 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
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2006.05.028

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.