Increased opioid inhibition of GABA release in nucleus accumbens during morphine withdrawal

Billy Chieng, John T. Williams

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

The nucleus accumbens is a key component of the reward pathway that plays a role in addiction to many drugs of abuse, including psychostimulants and opioids. The effects of withdrawal from chronic morphine were examined in the nucleus accumbens using brain slices from morphine-treated animals. Recordings were made from interneurons in the shell of nucleus accumbens, and the presynaptic inhibition of GABA-A IPSCs by opioids was examined. In slices from control animals, opioids caused a maximal inhibition of 50%, forskolin increased the IPSC amplitude by less than twofold, and the maximal inhibition by opioids in the presence of forskolin was not changed. During withdrawal, however, forskolin caused approximately a fourfold increase in the amplitude of the IPSC, and the maximal inhibition by opioids was increased to 80%. The results indicate that transmitter release is increased during opioid withdrawal, particularly after the activation of adenylyl cyclase. The cAMP- dependent increase in transmitter release is potently inhibited by opioids, such that the overall effect of opioids is augmented during withdrawal. The induction of an opioid-sensitive cAMP-dependent mechanism that regulates transmitter release may be a critical component of acute opioid withdrawal.

Original languageEnglish (US)
Pages (from-to)7033-7039
Number of pages7
JournalJournal of Neuroscience
Volume18
Issue number17
StatePublished - Sep 1 1998

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Keywords

  • A-kinase
  • Adenosine
  • Adenylyl cyclase
  • CAMP
  • Electrophysiology
  • μ-opioid

ASJC Scopus subject areas

  • Neuroscience(all)

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