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

Rachel J. Smith, Pouya Tahsili-Fahadan, Gary Aston-Jones

Research output: Contribution to journalArticle

103 Scopus citations


Orexin/hypocretin signaling at the orexin 1 receptor (OX1R) 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 OX1R 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 OX1R is critical for conditioned cocaine-seeking elicited by a drug-associated context, following either extinction or abstinence.

Original languageEnglish (US)
Pages (from-to)179-184
Number of pages6
Issue number1
StatePublished - Jan 1 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Pharmacology


  • Abstinence
  • Addiction
  • Cocaine
  • Orexin
  • Reinstatement
  • Self-administration

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