Reinstatement of ethanol-seeking behavior following intravenous self-administration in Wistar rats

Justin T. Gass, M. Foster Olive

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Background: In animal models of alcoholism, subjects are traditionally trained to self-administer ethanol via the oral route. However, ethanol is also self-administered intravenously (IV), a paradigm which offers several advantages over oral self-administration methods, including immediate delivery to the bloodstream, more rapid onset of pharmacological effects, and elimination of the need to utilize tastants or sweeteners to mask the aversive orosensory properties of ethanol. However, no studies to date have examined reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration. Methods: Male Wistar rats were implanted with indwelling jugular vein catheters and trained to self-administer ethanol IV (1% v/v solution, equivalent to 1 mg/kg) in an operant lever-pressing paradigm in twice daily 1 hour sessions. Each IV delivery of ethanol was paired with presentation of a light-tone complex stimulus. After stabilization of response patterns, IV self-administration behavior was subjected to extinction procedures. Next, animals were exposed to the three types of stimuli known to reinstate ethanol-seeking behavior: presentation of ethanol-associated cues, a priming dose of ethanol (0.5 g/kg i.p.), or exposure to stress via administration of the anxiogenic compound yohimbine (2.5 mg/kg i.p.) or its corresponding vehicle. Results: During the maintenance phase of self-administration, animals exhibited significantly more presses on the lever that delivered the ethanol solution than the inactive lever, indicating that IV ethanol functioned as a positive reinforcer. Following extinction, it was found that ethanol-seeking behavior could be reinstated by all three types of stimuli (cues, ethanol priming, and yohimbine). Vehicle injection did not affect responding on either lever. Conclusions: Ethanol serves as a reinforcer when self-administered IV, and following extinction, ethanol-seeking behavior can be reinstated by ethanol-associated cues, ethanol priming, or a pharmacological stressor. Thus, reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration may be a novel animal model of relapse.

Original languageEnglish (US)
Pages (from-to)1441-1445
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Issue number9
StatePublished - Sep 2007
Externally publishedYes


  • Conditioned Cues
  • Ethanol Priming
  • Intravenous
  • Pharmacological Stressor
  • Reinstatement
  • Relapse
  • Wistar Rat

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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