Effects of opioid receptor blockade on the renewal of alcohol seeking induced by context: relationship to c-fos mRNA expression

Eur J Neurosci. 2007 Nov;26(10):2815-23. doi: 10.1111/j.1460-9568.2007.05898.x.


Contextual stimuli associated with alcohol availability can induce alcohol seeking during abstinence. Using a renewal procedure, we tested the effect of opioid receptor blockade on context-induced alcohol seeking, and its relationship to the activity of brain sites involved in learning and reward. Thirty-six male Wistar rats were trained to lever press for a 12% (w/v) alcohol solution before undergoing extinction sessions (no alcohol delivery). Half of the rats underwent training, extinction and testing in a single context with a distinct set of olfactory, visual, auditory and tactile properties [training, extinction and test in Context A (AAA)]. The other half were trained and extinguished in different contexts and returned to the training context on the test day [training, extinction and test in Contexts A, B and A, respectively (ABA)]. On the test day, the rats from each condition were pre-treated with either saline or 1 mg/kg naltrexone (s.c.) and tested for alcohol seeking. Immediately following the test session, rats were killed and their brains were analysed for c-fos mRNA expression using in-situ hybridization. Re-exposure to the alcohol-associated context (ABA) significantly increased operant behaviour on the previously active lever relative to the AAA groups and this increased responding was associated with increased c-fos mRNA expression in the basal and lateral amygdala and the CA3 subregion of the hippocampus. Naltrexone pre-treatment attenuated context-induced alcohol seeking and inhibited c-fos mRNA expression in the lateral amygdala and CA3. Our findings point to a critical role for the basolateral amygdala and dorsal hippocampus in mediating context-induced renewal of alcohol seeking and suggest that opioidergic mechanisms mediate this effect.

Publication types

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

MeSH terms

  • Alcohol-Related Disorders / etiology
  • Alcohol-Related Disorders / psychology*
  • Alcohols / administration & dosage
  • Analysis of Variance
  • Animals
  • Autoradiography
  • Behavior, Animal / physiology
  • Brain / metabolism
  • Brain / pathology
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology*
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Male
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Physical Stimulation / methods
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism*
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Opioid / physiology*
  • Self Administration / methods


  • Alcohols
  • Narcotic Antagonists
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptors, Opioid
  • Naltrexone