CoChat
Sign Up
Cited by 13Neurotransmitter Receptor Influence on BehaviorReceptor Mechanisms and SignalingNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record.

Sustained treatment with a 5-HT2A receptor agonist causes functional desensitization and reductions in agonist-labeled 5-HT2A receptors despite increases in receptor protein levels in rats

Open access
Shi, Ju, Landry, Michelle, Carrasco, Gonzalo A., Battaglia, George, Muma, Nancy A.·2008·Neuropharmacology
DOI 10.1016/j.neuropharm.2008.06.001PMC PMC2578842
Open this paper in CoChat — free account

Abstract

Adaptive changes in serotonin2A (5-HT(2A)) receptor signaling are associated with the clinical response to a number of psychiatric drugs including atypical antipsychotics and selective serotonin reuptake inhibitors. The present study examined possible mechanisms of agonist-induced desensitization of 5-HT(2A) receptors in rat hypothalamic paraventricular nucleus (PVN) after 4 and 7 days of treatment with 1mg/kg (-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). The magnitude of 5-HT(2A) receptor-mediated oxytocin release decreased 78% after 4 days and 61% after 7 days of DOI treatment. Similarly, the magnitude of ACTH release following 1mg/kg DOI decreased by 31% after 4 days and 38% after 7 days of DOI treatment. Treatment with DOI for either 4 or 7 days caused a significant decrease (by approximately 50%) in the high-affinity 5-HT(2A) receptor binding as measured by (125)I-DOI binding compared to saline-treated control rats. In contrast, western blot analysis demonstrated a significant increase in 5-HT(2A) receptor protein levels with 4 or 7 days of DOI treatment to 167% and 191% of control levels, respectively. Real time quantitative RT-PCR analysis revealed a small but nonsignificant increase in the levels of 5-HT(2A) mRNA following treatment with DOI for 4 or 7 days. Taken together, the 5-HT(2A) receptor-stimulated hormone responses, agonist binding data and western blot data suggest that although agonist treatment increases the levels of 5-HT(2A) receptor protein in the cell membrane, there is a reduction in the population of 5-HT(2A) receptors capable of high-affinity binding and mediating a functional response.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.neuropharm.2008.06.001

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 32

  1. Akiyoshi, 1993, Paradoxical increase of 5-hydroxytryptamine2 receptors and 5-hydroxytryptamine2 receptor mRNA in cerebellar granule cells after persistent 5-hydroxytryptamine2 receptor stimulation, Mol. Pharmacol., 43, 349, 10.1016/S0026-895X(25)13620-1 · DOI
  2. Appel, 1990, Autoradiographic characterization of (±)-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane ([125I]DOI) binding to 5-HT2 and 5-HT1c receptors in rat brain, J. Pharmacol. Exp. Ther., 255, 843
  3. Damjanoska, 2004, Agonist-induced serotonin2A receptor desensitization in the rat frontal cortex and hypothalamus, J. Pharmacol. Exp. Ther., 309, 1043, 10.1124/jpet.103.062067 · DOI
  4. Damjanoska, 2003, Chronic fluoxetine differentially affects 5-HT2A receptor signaling in frontal cortex, oxytocin and corticotropin releasing factor (CRF)-containing neurons in rat paraventricular nucleus, J. Pharmacol. Exp. Ther., 306, 563, 10.1124/jpet.103.050534 · DOI
  5. Dean, 1996, Decreased frontal cortical serotonin2A receptors in schizophrenia, Schizophr Res, 21, 133, 10.1016/0920-9964(96)00034-5 · DOI
  6. Gray, 2003, Identification of two serine residues essential for agonist-induced 5-HT2A receptor desensitization, Biochemistry, 42, 10853, 10.1021/bi035061z · DOI
  7. Gray, 2001, Paradoxical trafficking and regulation of 5HT2A receptors by agonists and antagonists, Brain Res. Bull., 56, 441, 10.1016/S0361-9230(01)00623-2 · DOI
  8. Grotewiel, 1994, Regulation of serotonin2A receptors in heterologous expression systems, J. Neurochem., 63, 1255, 10.1046/j.1471-4159.1994.63041255.x · DOI
  9. Gundlah, 1999, Ovarian steroid effects on serotonin1A, 2A and 2C receptor mRNA in macaque hypothalamus, Brain Res. Mol. Brain Res., 63, 325, 10.1016/S0169-328X(98)00295-2 · DOI
  10. Hemrick-Luecke, 2002, Comparison of the potency of MDL 100,907 and SB 242084 in blocking the serotonin 5-HT2 receptor agonst-induced increases in rat serum corticosterone concentrations: evidence for 5-HT2A receptor mediation of the HPA axis, Neuropharmacology, 42, 162, 10.1016/S0028-3908(01)00166-6 · DOI
  11. Herman, 1997, Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis, Trends Neurosci., 20, 78, 10.1016/S0166-2236(96)10069-2 · DOI · Paper page
  12. Kindlundh-Hogberg, 2006, Quantitative mapping shows that serotonin rather than dopamine receptor mRNA expressions are affected after repeated intermittent administration of MDMA in rat brain, Neuropharmacology, 51, 838, 10.1016/j.neuropharm.2006.05.026 · DOI
  13. Kuoppamaki, 1995, Differential regulation of rat 5-HT2A and 5-HT2C receptors after chronic treatment with clozapine, chlorpromazine and three putative atypical antipsychotic drugs, Neuropsychopharmacology, 13, 139, 10.1016/0893-133X(95)00049-J · DOI
  14. Leonhardt, 1992, Molecular pharmacological differences in the interaction of serotonin with 5-hydroxytryptamine1C and 5-hydroxytryptamine2 receptors, Mol. Pharmacol., 42, 328, 10.1016/S0026-895X(25)08918-7 · DOI
  15. Lerer, 1999, 5-HT1A receptor function in normal subjects on clinical doses of fluoxetine: blunted temperature and hormone responses to ipsapirone challenge, Neuropsychopharmacology, 20, 628, 10.1016/S0893-133X(98)00106-7 · DOI
  16. Li, 1993, Long-term treatment with the antidepressants fluoxetine and desipramine potentiates endocrine responses to the serotonin agonists 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) and (±)-1- (2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI (DOI), J. Pharmacol. Exp. Ther., 266, 836
  17. Li, 1997, A desensitization of hypothalamic 5-HT1A receptors by repeated injections of paroxetine: reduction in the levels of Gi and Go proteins and neuroendocrine responses, but not in the density of 5-HT1A receptors, J. Pharmacol. Exp. Ther., 282, 1581, 10.1016/S0022-3565(24)36965-4 · DOI
  18. McKenna, 1989, Chronic treatment with (±)DOI, a psychotomimetic 5-HT2 agonist, downregulates 5-HT2 receptors in rat brain, Neuropsychopharmacology, 2, 81, 10.1016/0893-133X(89)90010-9 · DOI · Paper page
  19. Roth, 1991, Chronic mianserin treatment decreases 5-HT2 receptor binding without altering 5-HT2 receptor mRNA levels, Eur. J. Pharmacol., 207, 169, 10.1016/0922-4106(91)90093-W · DOI
  20. Roth, 1995, 5-Hydroxytryptamine2A (5-HT2A) receptor desensitization can occur without down-regulation, J. Pharmacol. Exp. Ther., 275, 1638
  21. Saphier, 1986, Electrophysiology of limbic forebrain and paraventricular nucleus connections, Brain Res. Bull., 17, 743, 10.1016/0361-9230(86)90085-7 · DOI
  22. Serres, 2000, Evidence that Gz proteins couple to hypothalamic 5-HT1A receptors in vivo, J. Neurosci., 20, 3095, 10.1523/JNEUROSCI.20-09-03095.2000 · DOI
  23. Shi, 2007, Agonist induced-phosphorylation of Galpha11 protein reduces coupling to 5-HT2A receptors, J. Pharmacol. Exp. Ther., 323, 248, 10.1124/jpet.107.122317 · DOI
  24. Shi, 2007, Phosphorylation of Galpha11 protein contributes to agonist-induced desensitization of 5-HT2A receptor signaling, Mol. Pharmacol., 71, 303, 10.1124/mol.106.028241 · DOI
  25. Singh, 2007, Olanzapine increases RGS7 protein expression via stimulation of the Janus tyrosine kinase-signal transducer and activator of transcription signaling cascade, J. Pharmacol. Exp. Ther., 322, 133, 10.1124/jpet.107.120386 · DOI
  26. Tilakaratne, 1995, Chronic fluoxetine or desmethylimipramine treatment alters 5-HT2 receptor mediated c-fos gene expression, Eur. J. Pharmacol. Mol. Pharmacol., 290, 263, 10.1016/0922-4106(95)90003-9 · DOI
  27. Van de Kar, 2001, 5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells, J. Neurosci., 21, 3572, 10.1523/JNEUROSCI.21-10-03572.2001 · DOI
  28. Van Wijngaarden, 1990, The concept of selectivity in 5-HT receptor research, Eur. J. Pharmacol., 188, 301, 10.1016/0922-4106(90)90190-9 · DOI
  29. Wright, 1995, Comparative localization of serotonin1A, 1C, and 2 receptor subtype mRNAs in rat brain, Brain Res. Bull., 351, 357
  30. Zea-Ponce, 2002, Pharmacokinetics and brain distribution in non human primate of R(-)[123I]DOI, A 5HT(2A/2C) serotonin agonist, Nucl. Med. Biol., 29, 575, 10.1016/S0969-8051(02)00306-2 · DOI · Paper page
  31. Zhang, 2001, Characterization of the functional heterologous desensitization of hypothalamic 5-HT1A receptors after 5-HT2A receptor activation, J. Neurosci., 21, 7919, 10.1523/JNEUROSCI.21-20-07919.2001 · DOI
  32. Zhang, 2002, Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (−)DOI, J. Neurosci., 22, 9635, 10.1523/JNEUROSCI.22-21-09635.2002 · DOI · Paper page

Cited by

Sorted by citations

Metadata

Authors
Shi, J., Landry, M., Carrasco, G. A., Battaglia, G., & Muma, N. A.
Affiliations
  • Loyola University Chicago (US)
  • University of Kansas (US)
Corresponding author
Muma, Nancy A.
ORCID
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2008-10
Volume
55
Issue
5
Pages
687-692
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2008.06.001
PMC
PMC2578842
OpenAlex
W2094612490
Cited by
13
References
0
Citations by year
2026: 2 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 2 · 2016: 1 · 2015: 1
FWCI
0.14
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Public Health Service
  • National Institute of Mental Health (MH068612, R01MH068612)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
5-HT2A receptor, receptor desensitization, digital object identifiers, serotonin receptor signaling, oxytocin release, ACTH release, paraventricular nucleus, receptor protein levels, receptor mRNA expression, atypical antipsychotics
MeSH terms
Adrenocorticotropic Hormone, Amphetamines, Analysis of Variance, Animals, Autoradiography, Body Weight, Dose-Response Relationship, Drug, Drug Administration Schedule, Gene Expression Regulation, Iodine Isotopes, Male, Oxytocin, Paraventricular Hypothalamic Nucleus, Protein Binding, RNA, Messenger, Time Factors, Rats, Sprague-Dawley, Serotonin Receptor Agonists, Receptor, Serotonin, 5-HT2A, Rats

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