Anterior thalamic paraventricular nucleus is involved in intermittent access ethanol drinking: role of orexin receptor 2

Addict Biol. 2015 May;20(3):469-81. doi: 10.1111/adb.12139. Epub 2014 Apr 9.


The paraventricular nucleus of the thalamus (PVT) has been shown to participate in hedonic feeding and is thought to influence drug seeking. This understudied nucleus contains anterior (aPVT) and posterior (pPVT) subregions, which receive dense projections from hypothalamic orexin/hypocretin (OX) but exhibit anatomical and functional differences. This study sought to characterize in Long-Evans rats the involvement of these PVT subregions and their OX receptor activity in consumption of the drug, ethanol. Compared with those maintained on water and chow only (water group), rats trained to drink pharmacologically relevant levels of ethanol (ethanol group) showed increased neuronal activation in the PVT, specifically the aPVT but not pPVT, as indicated by c-Fos immunoreactivity. Similar results were obtained in rats administered ethanol via oral gavage, indicating that this site-specific effect was due to ethanol exposure. In support of the involvement of OX, the ethanol group also showed increased mRNA levels of this neuropeptide in the hypothalamus and of OX 2 receptor (OX2R) but not OX 1 receptor (OX1R), again in the aPVT but not pPVT. Similarly, ethanol gavage increased double labeling of c-Fos with OX2R but not OX1R, specifically in the aPVT. Evidence directly supporting a role for aPVT OX2R in ethanol consumption was provided by results with local injections, showing ethanol intake to be enhanced by OX-A or OX-B in the aPVT but not pPVT and reduced by a local antagonist of OX2R but not OX1R. These results focus attention on the aPVT and specifically its OX2R in mediating a positive feedback relationship with ethanol intake.

Keywords: c-Fos; emotional behavior; immunohistochemistry; intermittent access; microinjection; rat.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / physiopathology*
  • Alcohol Drinking / prevention & control
  • Animals
  • Central Nervous System Depressants / pharmacology
  • Ethanol / pharmacology
  • Feedback, Psychological / physiology
  • Hypothalamus / metabolism
  • Isoquinolines / pharmacology
  • Male
  • Neurons / metabolism
  • Orexin Receptor Antagonists / pharmacology
  • Orexin Receptors / drug effects
  • Orexin Receptors / physiology*
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / physiology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Pyridines / pharmacology
  • Rats, Long-Evans
  • Reinforcement Schedule
  • Sucrose / pharmacology
  • Sweetening Agents / pharmacology
  • Up-Regulation / drug effects


  • 1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3,3-dimethyl-2-((4-pyridinylmethyl)amino)-1-butanone
  • Central Nervous System Depressants
  • Isoquinolines
  • Orexin Receptor Antagonists
  • Orexin Receptors
  • Proto-Oncogene Proteins c-fos
  • Pyridines
  • Sweetening Agents
  • Ethanol
  • Sucrose