Opiate withdrawal-induced fos immunoreactivity in the rat extended amygdala parallels the development of conditioned place aversion

Neuropsychopharmacology. 2001 Feb;24(2):152-60. doi: 10.1016/S0893-133X(00)00186-X.


Low doses of naloxone have been shown to affect the motivational aspects of opiate withdrawal in morphine-dependent rats. Conditioned place aversion to opiate withdrawal is one of the most sensitive of motivational indices of opiate withdrawal and is thought to be mediated by the basal forebrain. Expression of the transcription factor Fos is known to increase during opiate withdrawal, but its presence during low-dose antagonist-precipitated withdrawal has not previously been established. In order to determine if there is a relationship between withdrawal-induced neuronal activity and conditioned place aversion, immunocytochemical localization of Fos was examined in the basal forebrain of opiate-dependent animals receiving one of several doses of naloxone (0, 3.25, 7.5, 15, 30, or 1000 microg/kg). In separate groups of opiate-dependent animals, naloxone doses of 3.25 - 30 microg/kg were paired with a specific chamber in a single-pairing conditioned place aversion paradigm. Significant increases in both immunocytochemical detection of Fos and conditioned place aversion were seen at doses >/= 7.5 microg/kg. The shell of the nucleus accumbens and central nucleus of the amygdala were most sensitive to low doses, thus supporting the hypothesis that the extended amygdala plays a role in opiate-induced condition place aversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects*
  • Amygdala / metabolism
  • Animals
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Male
  • Naloxone / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Opioid-Related Disorders / metabolism
  • Proto-Oncogene Proteins c-fos / drug effects*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Wistar
  • Substance Withdrawal Syndrome / metabolism*


  • Narcotic Antagonists
  • Proto-Oncogene Proteins c-fos
  • Naloxone