dc.contributor.author | Zhang, Yahong | |
dc.contributor.author | D'Souza, Deborah N. | |
dc.contributor.author | Raap, Danı́ K. | |
dc.contributor.author | Garcia, Francisca | |
dc.contributor.author | Battaglia, George | |
dc.contributor.author | Muma, Nancy A. | |
dc.contributor.author | Van de Kar, Louis D. | |
dc.date.accessioned | 2015-05-11T17:25:21Z | |
dc.date.available | 2015-05-11T17:25:21Z | |
dc.date.issued | 2001-10-15 | |
dc.identifier.citation | Zhang, Y., D'Souza, D., Raap, D. K., Garcia, F., et al. (2001) Characterization of the functional heterologous desensitization of hypothalamic 5-HT1A receptors after 5-HT2A receptor activation. J. Neurosci, 21(20), 7919-7927. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17696 | |
dc.description | This is the publisher's version, also available electronically from "www.jneurosci.org". | en_US |
dc.description.abstract | Desensitization of 5-HT1A receptors could be involved in the long-term therapeutic effect of anxiolytic and antidepressant drugs. Pretreatment of rats with the 5-HT2A/2C agonist DOI induces an attenuation of hypothalamic 5-HT1Areceptor–Gz-protein signaling, measured as the ACTH and oxytocin responses to an injection of the 5-HT1A agonist 8-OH-DPAT. We characterized this functional heterologous desensitization of 5-HT1A receptors in rats and examined some of the mechanisms that are involved. A time course experiment revealed that DOI produces a delayed and reversible reduction of the ACTH and oxytocin responses to an 8-OH-DPAT challenge. The maximal desensitization occurred at 2 hr, and it disappeared 24 hr after DOI injection. The desensitization was dose-dependent, and it shifted the oxytocin and ACTH dose–response curves of 8-OH-DPAT to the right (increased ED50) with no change in their maximal responses (E max). The 5-HT2A receptor antagonist MDL 100,907 prevented the DOI-induced desensitization, indicating that 5-HT2Areceptors mediate the effect of DOI. Analysis of the components of the 5-HT1A receptor–Gz-protein signaling system showed that DOI did not alter the level of membrane-associated Gz-proteins in the hypothalamus. Additionally, DOI did not alter the binding of [3H]8-OH-DPAT or the inhibition by GTPγS of [3H]8-OH-DPAT binding in the hypothalamus. In conclusion, the activation of 5-HT2Areceptors induces a transient functional desensitization of 5-HT1A receptor signaling in the hypothalamus, which may occur distal to the 5-HT1A receptor–Gz-protein interface. | en_US |
dc.publisher | Society for Neuroscience | en_US |
dc.relation.isversionof | http://www.jneurosci.org/content/21/20/7919 | en_US |
dc.title | Characterization of the functional heterologous desensitization of hypothalamic 5-HT1A receptors after 5-HT2A receptor activation | en_US |
dc.type | Article | |
kusw.kuauthor | Muma, Nancy A. | |
kusw.kudepartment | Pharmacology & Toxicology | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess | |