Increased probability of GABA release during withdrawal from morphine

Antonello Bonci, John T. Williams

Research output: Contribution to journalArticle

209 Scopus citations

Abstract

Opioid receptors located on interneurons in the ventral tegmental area (VTA) inhibit GABA(A)-mediated synaptic transmission to dopamine projection neurons. The resulting disinhibition of dopamine cells in the VTA is thought to play a pivotal role in drug abuse; however, little is known about how this GABA(A) synapse is affected after chronic morphine treatment. The regulation of GABA release during acute withdrawal from morphine was studied in slices from animals treated for 6-7 d with morphine. Slices containing the VTA were prepared and maintained in morphine-free solutions, and GABA(A) IPSCs were recorded from dopamine cells. The amplitude of evoked IPSCs and the frequency of spontaneous miniature IPSCs measured in slices from morphine-treated guinea pigs were greater than placebo-treated controls. In addition, activation of adenylyl cyclase, with forskolin, and cAMP-dependent protein kinase, with Sp-cAMPS, caused a larger increase in IPSCs in slices from morphine-treated animals. Conversely, the kinase inhibitors staurosporine and Rp-CPT-cAMPS decreased GABA IP-SCs to a greater extent after drug treatment. The results indicate that the probability of GABA release was increased during withdrawal from chronic morphine treatment and that this effect resulted from an upregulation of the cAMP-dependent cascade. Increased transmitter release from opioid-sensitive synapses during acute withdrawal may be one adaptive mechanism that results from prolonged morphine treatment.

Original languageEnglish (US)
Pages (from-to)796-803
Number of pages8
JournalJournal of Neuroscience
Volume17
Issue number2
DOIs
StatePublished - 1997

Keywords

  • A-kinase
  • GABA(A)
  • cAMP
  • dopamine
  • tolerance
  • ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

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