Orexin/hypocretin is necessary for context-driven cocaine-seeking

Neuropharmacology. 2010 Jan;58(1):179-84. doi: 10.1016/j.neuropharm.2009.06.042. Epub 2009 Jul 8.

Abstract

Orexin/hypocretin signaling at the orexin 1 receptor (OX(1)R) has recently been implicated in addiction and relapse. We examined the role of the orexin system in cocaine-seeking elicited by a drug-associated context following abstinence or extinction from chronic cocaine self-administration. Male Sprague-Dawley rats self-administered cocaine in 2-h sessions for 10 days, followed by extinction training or extended abstinence in the home cage. The OX(1)R antagonist SB-334867 (SB; 10, 20, or 30 mg/kg, i.p.) was administered prior to re-exposure to the cocaine self-administration environment. We found that pretreatment with SB significantly attenuated cocaine-seeking when rats were placed back into the self-administration environment following either 1 day or 2 weeks of abstinence (no extinction), or following extinction of cocaine-seeking in an alternative environment (distinct from the training environment). These results indicate that orexin signaling at OX(1)R is critical for conditioned cocaine-seeking elicited by a drug-associated context, following either extinction or abstinence.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzoxazoles / pharmacology
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / metabolism*
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / drug effects
  • Disease Models, Animal
  • Extinction, Psychological / physiology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Naphthyridines
  • Neuropeptides / metabolism*
  • Orexin Receptors
  • Orexins
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Reinforcement, Psychology*
  • Self Administration
  • Time Factors
  • Urea / analogs & derivatives
  • Urea / pharmacology

Substances

  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Intracellular Signaling Peptides and Proteins
  • Naphthyridines
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Urea
  • Cocaine