Molecular components of tolerance to opiates in single hippocampal neurons

T. Bushell, T. Endoh, A.A. Simen, D. Ren, V.P. Bindokas, R.J. Miller

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35 Citations (Scopus)

Abstract

We examined the effect of acute and chronic opioid treatment on synaptic transmission and µ-opioid receptor (MOR) endocytosis in cultures of naïve rat hippocampal neurons. Opioid agonists that activate MOR inhibited synaptic transmission at inhibitory but not excitatory autapses. [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), morphine, and methadone were all effective at blocking inhibitory transmission. These same drugs also reduced the amplitude of voltage-dependent Ca2+ currents in inhibitory but not excitatory neurons. Chronic treatment with all three opioids reduced the subsequent effects of a challenge with either the same drug or one of the others in individual autaptic neurons. Chronic treatment with DAMGO or methadone produced internalization of enhanced yellow fluorescent protein-tagged MOR expressed in hippocampal neurons within hours, whereas morphine produced internalization much more slowly, even when accompanied by overexpression of beta -arrestin-2. We conclude that DAMGO, methadone, and morphine all produce tolerance in single hippocampal neurons. Morphine-induced tolerance does not necessarily seem to involve receptor endocytosis.
Original languageEnglish
Pages (from-to)55-64
Number of pages9
JournalMolecular Pharmacology
Volume61
Issue number1
DOIs
Publication statusPublished - 2002

Keywords

  • pharmacology
  • biomedicine
  • opiates
  • physiology

Cite this

Bushell, T., Endoh, T., Simen, A. A., Ren, D., Bindokas, V. P., & Miller, R. J. (2002). Molecular components of tolerance to opiates in single hippocampal neurons. Molecular Pharmacology, 61(1), 55-64. https://doi.org/10.1124/mol.61.1.55