Microdialysis evidence that acetylcholine in the nucleus accumhens is involved in morphine withdrawal and its treatment with clonidine

Pedro Rada, Emmanuel Pothos, Gregory Mark, Bartley G. Hoebel

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This study used microdialysis to measure changes in extracellular acetylcholine (ACh) content in the nucleus accumbens (NAC) of freely moving rats during acute and chronic morphine treatment, and following naloxone-precipitated withdrawal. Morphine injection (20 mg/kg, i.p.) caused a significant decrease in extracellular ACh which was not apparent after repeated exposure to the opiate for 7 days. Basal recovery of ACh was not altered by chronic morphine treatment. On day 8, after morphine dependence had been established, naloxone caused a large increase in ACh levels accompanied by withdrawal symptoms such as wet dog shakes, diarrhea and teeth-chattering. Pretreatment with clonidine (200 μg/kg, i.p.) reduced these withdrawal symptoms and eliminated the ACh response. These results suggest that accumbens ACh is involved in some of the aversive aspects of opiate withdrawal.

Original languageEnglish (US)
Pages (from-to)354-356
Number of pages3
JournalBrain Research
Issue number2
Publication statusPublished - Oct 11 1991
Externally publishedYes



  • Acetylcholine
  • Microdialysis
  • Morphine
  • Naloxone
  • Nucleus Accumbens
  • Opiate
  • Rat

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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