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
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“genetic knockout of adenylyl cyclase type 5 in mice prevents the reward response to opioids such as morphine [81].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [81]
Citations
Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
mouse brain in stereotaxic coordinates
Franklin, K. B. J., & Paxinos, G. (1997) · Cited by 3,258
Matthes, H. W. D., Maldonado, R., Simonin, F., Valverde, O., Slowe, S., Kitchen, I., Befort, K., Dierich, A., Le Meur, M., Dollé, P., et al. (1996) · Nature · doi:10.1038/383819a0 · Cited by 1,722
Molecular and Cellular Basis of Addiction
Nestler, E. J., & Aghajanian, G. K. (1997) · Science · doi:10.1126/science.278.5335.58 · Cited by 1,295
Self-citationKoob, G. F., Sanna, P. P., & Bloom, F. E. (1998) · Neuron · doi:10.1016/s0896-6273(00)80557-7 · Cited by 1,026
Neuroanatomy of the pain system and of the pathways that modulate pain
Willis, W. D., & Westlund, K. N. (1997) · Journal of Clinical Neurophysiology · doi:10.1097/00004691-199701000-00002 · Cited by 924
Complexity and Diversity of Mammalian Adenylyl Cyclases
Sunahara, R. K., Dessauer, C. W., & Gilman, A. G. (1996) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.36.040196.002333 · Cited by 874
Mu, delta, and kappa opioid receptor mRNA expression in the rat CNS: An in situ hybridization study
Mansour, A., Fox, C. A., Burke, S., Meng, F., Thompson, R. C., Akil, H., & Watson, S. J. (1994) · The Journal of Comparative Neurology · doi:10.1002/cne.903500307 · Cited by 872
Kelley, A. E. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.016 · Cited by 788
Drug-activation of brain reward pathways
Wise, R. A. (1998) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(98)00063-5 · Cited by 684
Research works printed but not linked: 2
- T. W. Robbins, B. J. Everitt Learn. Mem 78, 625–636 (2002).
- L. Y. Li, K. J. Chang Mol. Pharmacol 50, 599–602 (1996).
Cited by
Sorted by citations
Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders
O’Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., et al. (2012) · Science · doi:10.1126/science.1227764 · Cited by 1,240
Molecular mechanisms of opioid receptor-dependent signaling and behavior
Al-Hasani, R., & Bruchas, M. R. (2011) · Anesthesiology · doi:10.1097/aln.0b013e318238bba6 · Cited by 1,067
Sadana, R., & Dessauer, C. W. (2009) · Neurosignals · doi:10.1159/000166277 · Cited by 361
Dichter, G. S., Damiano, C. A., & Allen, J. A. (2012) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-4-19 · Cited by 299
Capturing adenylyl cyclases as potential drug targets
Pierre, S. C., Eschenhagen, T., Geißlinger, G., & Scholich, K. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2827 · Cited by 233
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)
- 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
- 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
- green
- europepmc.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
