Orexin signaling in rostral lateral hypothalamus and nucleus accumbens shell in the control of spontaneous physical activity in high- and low-activity rats

Claudio Perez-Leighton, Morgan R. Little, Martha Grace, Charles J Billington, Catherine M Kotz

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11 Scopus citations

Abstract

Spontaneous physical activity (SPA) describes activity outside of formal exercise and shows large interindividual variability. The hypothalamic orexin/hypocretin peptides are key regulators of SPA. Orexins drive SPA within multiple brain sites, including rostral lateral hypothalamus (LH) and nucleus accumbens shell (NAcSh). Rats with high basal SPA (high activity, HA) show higher orexin mRNA expression and SPA after injection of orexin-A in rostral LH compared with low-activity (LA) rats. Here, we explored the contribution of orexin signaling in rostral LH and NAcSh to the HA/LA phenotype. We found that HA rats have higher sensitivity to SPA after injection of orexin-A in rostral LH, but not in NAcSh. HA and LA rats showed similar levels of orexin receptor expression in rostral LH, and activation of orexin-producing neurons after orexin-A injection in rostral LH. Also, in HA and LA rats, the coinjection of orexin-A in rostral LH and NAcSh failed to further increase SPA beyond the effects of orexin-A in rostral LH. Pretreatment with muscimol, a GABAA receptor agonist, in NAcSh potentiated SPA produced by orexin-A injection in rostral LH in HA but not in LA rats. Our results suggest that a feedback loop from orexin-responsive neurons in rostral LH to orexin neurons and a the NAcSh-orexin neuron-rostral LH circuit regulate SPA. Overall, our data suggest that differences in orexin sensitivity in rostral LH and its modulation by GABA afferents from NAcSh contribute to individual SPA differences.

Original languageEnglish (US)
Pages (from-to)R338-R346
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume312
Issue number3
DOIs
StatePublished - Mar 2017

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grant R01 DK-100281-01A1 (to C. M. Kotz and C. J. Billington) and Grant CONICYT FONDECYT Regular 1150274 (to C. Perez-Leighton).

Publisher Copyright:
© 2017 the American Physiological Society.

Keywords

  • Accumbens
  • Lateral hypothalamus
  • Orexin
  • Physical activity
  • Spontaneous physical activity

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