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 Billington, Catherine M. Kotz

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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
Pages (from-to)R338-R346
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume312
Issue number3
DOIs
Publication statusPublished - Mar 2017

Keywords

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

ASJC Scopus subject areas

  • General Medicine

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