Circadian-dependent and circadian-independent behavioral actions of hypocretin/orexin

Brain Res. 2002 Jul 12;943(2):224-36. doi: 10.1016/s0006-8993(02)02653-7.


The hypocretins/orexins modulate behavioral state as well as a variety of state-dependent behaviors. Levels of hypocretin-1 and prepro-hypocretin mRNA vary in a circadian fashion, suggesting that hypocretin neurotransmission may vary across the circadian cycle. To better assess the circadian dependency of the behavioral actions of hypocretin-1, the behavioral effects of intracerebroventricular hypocretin-1 administration (3.0 nmol/2 microl) were examined at differing portions of the circadian cycle, when animals display either low levels of waking (light-period) or high levels of waking (dark-period). In addition, mediation analyses were conducted to better assess the contribution of the wake-promoting actions to other behavioral actions of hypocretin-1. During the light-period, hypocretin-1 administration increased time spent awake, grooming, feeding, locomotor activity and chewing of inedible material, a stress-related behavior. Comparable effects of hypocretin-1 on time spent awake, locomotor activity and the chewing of inedible material were observed during the dark-period. In contrast, hypocretin-1-induced feeding and drinking appeared largely circadian-dependent: hypocretin-1 had minimal effects on these behaviors during the dark-period. Hypocretin-1-induced increases in grooming appeared moderately circadian-dependent. These observations suggest that the previously described ability of hypocretin to increase feeding and drinking during the light-period may reflect, at least in part, a general behavioral activation associated with waking. Results from the mediation analyses support these conclusions, indicating that hypocretin-1-induced increases in waking largely account for hypocretin-1-induced increases in feeding and drinking. Additionally, given that chewing and grooming are stress-related behaviors, these observations provide further support for a possible function of HCRT in stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Dark Adaptation / drug effects
  • Dark Adaptation / physiology
  • Drinking Behavior / drug effects
  • Drinking Behavior / physiology
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology
  • Grooming / drug effects
  • Grooming / physiology
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism*
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Mastication / drug effects
  • Mastication / physiology
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Neuropeptides / pharmacology
  • Orexins
  • Photic Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Sleep / drug effects
  • Sleep / physiology
  • Stress, Physiological / physiopathology
  • Wakefulness / drug effects
  • Wakefulness / physiology*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins