Multiple roles for orexin/hypocretin in addiction

Stephen V. Mahler, Rachel J. Smith, David E. Moorman, Gregory C. Sartor, Gary Aston-Jones

Research output: Chapter in Book/Report/Conference proceedingChapter

145 Scopus citations


Orexins/hypocretins are hypothalamic peptides involved in arousal and wakefulness, but also play a critical role in drug addiction and reward-related behaviors. Here, we review the roles played by orexins in a variety of animal models of drug addiction, emphasizing both commonalities and differences for orexin's involvement in seeking of the major classes of abused drugs, as well as food. One common theme that emerges is an involvement of orexins in drug seeking triggered by external stimuli (e.g., cues, contexts or stressors). We also discuss the functional neuronal circuits in which orexins are embedded, and how these circuits mediate addiction-related behaviors, with particular focus on the role of orexin and glutamate interactions within the ventral tegmental area. Finally, we attempt to contextualize the role of orexins in reward by discussing ways in which these peptides, expressed in only a few thousand neurons in the brain, can have such wide-ranging effects on behavior.

Original languageEnglish (US)
Title of host publicationProgress in Brain Research
PublisherElsevier B.V.
Number of pages43
StatePublished - 2012

Publication series

NameProgress in Brain Research
ISSN (Print)0079-6123
ISSN (Electronic)1875-7855


  • Cocaine
  • Cues
  • Ethanol
  • Food
  • Glutamate
  • Motivation
  • Nicotine
  • Opiates

ASJC Scopus subject areas

  • Neuroscience(all)


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