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Molecular Pharmacology

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Research ArticleArticle

Molecular Components of Tolerance to Opiates in Single Hippocampal Neurons

T. Bushell, T. Endoh, A. A. Simen, D. Ren, V. P. Bindokas and R. J. Miller
Molecular Pharmacology January 2002, 61 (1) 55-64; DOI: https://doi.org/10.1124/mol.61.1.55
T. Bushell
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois
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T. Endoh
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois
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A. A. Simen
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois
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D. Ren
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois
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V. P. Bindokas
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois
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R. J. Miller
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois
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Abstract

We examined the effect of acute and chronic opioid treatment on synaptic transmission and μ-opioid receptor (MOR) endocytosis in cultures of naı̈ve 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 β-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.

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Molecular Pharmacology: 61 (1)
Molecular Pharmacology
Vol. 61, Issue 1
1 Jan 2002
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Research ArticleArticle

Molecular Components of Tolerance to Opiates in Single Hippocampal Neurons

T. Bushell, T. Endoh, A. A. Simen, D. Ren, V. P. Bindokas and R. J. Miller
Molecular Pharmacology January 1, 2002, 61 (1) 55-64; DOI: https://doi.org/10.1124/mol.61.1.55

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Research ArticleArticle

Molecular Components of Tolerance to Opiates in Single Hippocampal Neurons

T. Bushell, T. Endoh, A. A. Simen, D. Ren, V. P. Bindokas and R. J. Miller
Molecular Pharmacology January 1, 2002, 61 (1) 55-64; DOI: https://doi.org/10.1124/mol.61.1.55
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