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

C. M. Kotz, C. Wang, Jennifer A Teske, A. J. Thorpe, C. M. Novak, K. Kiwaki, J. A. Levine

Research output: Contribution to journalArticle

75 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalNeuroscience
Volume142
Issue number1
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Brain
Lateral Hypothalamic Area
Muscimol
Physical Stimulation
Obesity
Orexins
GABA Agonists
Dopamine Antagonists
Paraventricular Hypothalamic Nucleus
Substantia Nigra
Arousal
Neuropeptides
gamma-Aminobutyric Acid
Walking
Sprague Dawley Rats
Dopamine
Motor Activity
Pars Compacta
SCH 23390

Keywords

  • hypocretin
  • hypothalamic paraventricular nucleus
  • lateral hypothalamus
  • locomotor activity
  • orexin
  • substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kotz, C. M., Wang, C., Teske, J. A., Thorpe, A. J., Novak, C. M., Kiwaki, K., & Levine, J. A. (2006). Orexin A mediation of time spent moving in rats: Neural mechanisms. Neuroscience, 142(1), 29-36. https://doi.org/10.1016/j.neuroscience.2006.05.028

Orexin A mediation of time spent moving in rats : Neural mechanisms. / Kotz, C. M.; Wang, C.; Teske, Jennifer A; Thorpe, A. J.; Novak, C. M.; Kiwaki, K.; Levine, J. A.

In: Neuroscience, Vol. 142, No. 1, 2006, p. 29-36.

Research output: Contribution to journalArticle

Kotz, CM, Wang, C, Teske, JA, Thorpe, AJ, Novak, CM, Kiwaki, K & Levine, JA 2006, 'Orexin A mediation of time spent moving in rats: Neural mechanisms', Neuroscience, vol. 142, no. 1, pp. 29-36. https://doi.org/10.1016/j.neuroscience.2006.05.028
Kotz, C. M. ; Wang, C. ; Teske, Jennifer A ; Thorpe, A. J. ; Novak, C. M. ; Kiwaki, K. ; Levine, J. A. / Orexin A mediation of time spent moving in rats : Neural mechanisms. In: Neuroscience. 2006 ; Vol. 142, No. 1. pp. 29-36.
@article{614cd7404a3547b982e95dfd841e72fe,
title = "Orexin A mediation of time spent moving in rats: Neural mechanisms",
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.",
keywords = "hypocretin, hypothalamic paraventricular nucleus, lateral hypothalamus, locomotor activity, orexin, substantia nigra",
author = "Kotz, {C. M.} and C. Wang and Teske, {Jennifer A} and Thorpe, {A. J.} and Novak, {C. M.} and K. Kiwaki and Levine, {J. A.}",
year = "2006",
doi = "10.1016/j.neuroscience.2006.05.028",
language = "English (US)",
volume = "142",
pages = "29--36",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - Orexin A mediation of time spent moving in rats

T2 - Neural mechanisms

AU - Kotz, C. M.

AU - Wang, C.

AU - Teske, Jennifer A

AU - Thorpe, A. J.

AU - Novak, C. M.

AU - Kiwaki, K.

AU - Levine, J. A.

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - hypocretin

KW - hypothalamic paraventricular nucleus

KW - lateral hypothalamus

KW - locomotor activity

KW - orexin

KW - substantia nigra

UR - http://www.scopus.com/inward/record.url?scp=33748514540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748514540&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2006.05.028

DO - 10.1016/j.neuroscience.2006.05.028

M3 - Article

C2 - 16809007

AN - SCOPUS:33748514540

VL - 142

SP - 29

EP - 36

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 1

ER -