Role of orexin/hypocretin in reward-seeking and addiction

Implications for obesity

Angie M. Cason, Rachel J. Smith, Pouya Tahsili-Fahadan, David E. Moorman, Gregory Sartor, Gary Aston-Jones

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Orexins (also named hypocretins) are recently discovered neuropeptides made exclusively in the hypothalamus. Recent studies have shown that orexin cells located specifically in lateral hypothalamus (LH) are involved in motivated behavior for drugs of abuse as well as natural rewards. Administration of orexin has been shown to stimulate food consumption, and orexin signaling in VTA has been implicated in intake of high-fat food. In self-administration studies, the orexin 1 receptor antagonist SB-334867 (SB) attenuated operant responding for high-fat pellets, sucrose pellets and ethanol, but not cocaine, demonstrating that signaling at orexin receptors is necessary for reinforcement of specific rewards. The orexin system is also implicated in associations between rewards and relevant stimuli. For example, Fos expression in LH orexin neurons varied in proportion to conditioned place preference (CPP) for food, morphine, or cocaine. This Fos expression was altered accordingly for CPP administered during protracted abstinence from morphine or cocaine, when preference for natural rewards was decreased and drug preference was increased. Additionally, orexin has been shown to be involved in reward-stimulus associations in the self-administration paradigm, where SB attenuated cue-induced reinstatement of extinguished sucrose- or cocaine-seeking. Although the specific circuitry mediating the effects of orexin on food reward remains unknown, VTA seems likely to be a critical target for at least some of these orexin actions. Thus, recent studies have established a role for orexin in reward-based feeding, and further investigation is warranted for determining whether function/dysfunction of the orexin system may contribute to the overeating associated with obesity. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.

Original languageEnglish (US)
Pages (from-to)419-428
Number of pages10
JournalPhysiology and Behavior
Volume100
Issue number5
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Reward
Obesity
Cocaine
Lateral Hypothalamic Area
Self Administration
Food
Morphine
Sucrose
Orexin Receptors
Fats
Food Preferences
Hyperphagia
Street Drugs
Orexins
Neuropeptides
Hypothalamus
Cues
Ethanol
Neurons
Pharmaceutical Preparations

Keywords

  • Addiction
  • Conditioned stimuli
  • Obesity
  • Orexin
  • Palatable food
  • Reward-based feeding

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Experimental and Cognitive Psychology

Cite this

Cason, A. M., Smith, R. J., Tahsili-Fahadan, P., Moorman, D. E., Sartor, G., & Aston-Jones, G. (2010). Role of orexin/hypocretin in reward-seeking and addiction: Implications for obesity. Physiology and Behavior, 100(5), 419-428. https://doi.org/10.1016/j.physbeh.2010.03.009

Role of orexin/hypocretin in reward-seeking and addiction : Implications for obesity. / Cason, Angie M.; Smith, Rachel J.; Tahsili-Fahadan, Pouya; Moorman, David E.; Sartor, Gregory; Aston-Jones, Gary.

In: Physiology and Behavior, Vol. 100, No. 5, 07.2010, p. 419-428.

Research output: Contribution to journalArticle

Cason, AM, Smith, RJ, Tahsili-Fahadan, P, Moorman, DE, Sartor, G & Aston-Jones, G 2010, 'Role of orexin/hypocretin in reward-seeking and addiction: Implications for obesity', Physiology and Behavior, vol. 100, no. 5, pp. 419-428. https://doi.org/10.1016/j.physbeh.2010.03.009
Cason AM, Smith RJ, Tahsili-Fahadan P, Moorman DE, Sartor G, Aston-Jones G. Role of orexin/hypocretin in reward-seeking and addiction: Implications for obesity. Physiology and Behavior. 2010 Jul;100(5):419-428. https://doi.org/10.1016/j.physbeh.2010.03.009
Cason, Angie M. ; Smith, Rachel J. ; Tahsili-Fahadan, Pouya ; Moorman, David E. ; Sartor, Gregory ; Aston-Jones, Gary. / Role of orexin/hypocretin in reward-seeking and addiction : Implications for obesity. In: Physiology and Behavior. 2010 ; Vol. 100, No. 5. pp. 419-428.
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