Stimuli linked to ethanol availability activate hypothalamic CART and orexin neurons in a reinstatement model of relapse

Biol Psychiatry. 2008 Jan 15;63(2):152-7. doi: 10.1016/j.biopsych.2007.02.002. Epub 2007 Jun 13.


Background: There has been a recent upsurge of interest in the role of hypothalamic feeding peptides, in particular, orexin (hypocretin), in drug-seeking behavior. However, the potential role of other hypothalamic feeding peptides, such as cocaine- and amphetamine-regulated transcript (CART), in conditioned reinstatement has yet to be explored.

Methods: Animals were exposed to environmental stimuli previously associated with ethanol availability (EtOH S+), and sections from the hypothalamus and paraventricular thalamus (PVT), a recipient of CART and orexin innervation, were dual labeled for Fos-protein and either CART or orexin.

Results: Significantly larger numbers of Fos-positive arcuate nucleus CART and hypothalamic orexin neurons were seen in animals exposed to the EtOH S+ compared with nonreward S- animals. Presentation of the EtOH S+ also increased numbers of Fos-positive PVT neurons. Fos-positive PVT neurons were observed to be closely associated with orexin and CART terminal fields.

Conclusions: Taken together, these findings suggest that activation of hypothalamic neuropeptide systems may be a common mechanism underlying drug-seeking behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Central Nervous System Depressants / administration & dosage*
  • Conditioning, Operant / drug effects
  • Ethanol / administration & dosage*
  • Hypothalamus / cytology*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuropeptides / metabolism*
  • Orexins
  • Rats
  • Rats, Wistar


  • Central Nervous System Depressants
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Orexins
  • cocaine- and amphetamine-regulated transcript protein
  • Ethanol