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Cited by 123Neuropeptides and Animal PhysiologyReceptor Mechanisms and SignalingNeurotransmitter Receptor Influence on Behavior

The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.

Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action

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Kim, Kyoung-Shim, Lee, Ko-Woon, Lee, Kang-Woo, Im, Joo-Young, Yoo, Ji Yeoun, Kim, Seung-Woo, Lee, Ja-Kyeong, Nestler, Eric J., Han, Pyung-Lim·2006·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0508812103
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Abstract

Opioid drugs produce their pharmacological effects by activating inhibitory guanine nucleotide-binding regulatory protein-linked μ, δ, and κ opioid receptors. One major effector for these receptors is adenylyl cyclase, which is inhibited upon receptor activation. However, little is known about which of the ten known forms of adenylyl cyclase are involved in mediating opioid actions. Here we show that all of the major behavioral effects of morphine, including locomotor activation, analgesia, tolerance, reward, and physical dependence and withdrawal symptoms, are attenuated in mice lacking adenylyl cyclase type 5 (AC5), a form of adenylyl cyclase that is highly enriched in striatum. Furthermore, the behavioral effects of selective μ or δ opioid receptor agonists are lost in AC5 −/− mice, whereas the behavioral effects of selective κ opioid receptor agonists are unaffected. These behavioral data are consistent with the observation that the ability of a μ or δ opioid receptor agonist to suppress adenylyl cyclase activity was absent in striatum of AC5 −/− mice. Together, these results establish AC5 as an important component of μ and δ opioid receptor signal transduction mechanisms in vivo and provide further support for the importance of the cAMP pathway as a critical mediator of opioid action.

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Crossref · 10.1073/pnas.0508812103

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  1. T. W. Robbins, B. J. Everitt Learn. Mem 78, 625–636 (2002).
  2. L. Y. Li, K. J. Chang Mol. Pharmacol 50, 599–602 (1996).

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Metadata

Authors
Kim, K.-S., Lee, K.-W., Lee, K.-W., Im, J.-Y., Yoo, J. Y., Kim, S.-W., Lee, J.-K., Nestler, E. J., & Han, P.-L.
Affiliations
  • Ewha Womans University (KR)
  • Inha University (KR)
  • The University of Texas Southwestern Medical Center (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2006-02-28
Volume
103
Issue
10
Pages
3908-3913
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0508812103
OpenAlex
W2139496188
Cited by
123
References
51
Citations by year
2026: 1 · 2025: 2 · 2024: 6 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 10 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 5 · 2013: 7 · 2012: 13
FWCI
4.30
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
adenylyl cyclase type 5, morphine, opioid receptors, mu-opioid receptor, delta opioid receptor, kappa opioid receptor, striatum, cAMP signaling, opioid tolerance, opioid reward, opioid use disorder, opioid withdrawal, analgesia, locomotor activation
MeSH terms
Adenylyl Cyclases, Animals, Behavior, Animal, Conditioning, Psychological, Corpus Striatum, Isoenzymes, Mice, Inbred C57BL, Morphine, Motor Activity, Pain Measurement, Receptors, Opioid, Substance Withdrawal Syndrome, Signal Transduction, Receptors, Opioid, mu, Receptors, Opioid, delta, Mice, Knockout, Mice

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