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Differential regulation of 5-HT1A receptor-G protein interactions in brain following chronic antidepressant administration.

Authors: Hensler, JG 
Citation: Hensler JG Neuropsychopharmacology. 2002 May;26(5):565-73.
Pubmed: (View Article at PubMed) PMID:11927181
DOI: Full-text: DOI:10.1016/S0893-133X(01)00395-5

Changes in 5-HT(1A) receptor function or sensitivity following chronic antidepressant treatment may involve changes in receptor-G protein interaction. We have examined the effect of chronic administration of the SSRI fluoxetine or the tricyclic antidepressant amitriptyline on 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding in serotonergic cell body areas, and cortical and limbic structures using quantitative autoradiography. Treatment of rats with fluoxetine, but not amitriptyline, resulted in an attenuation of 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding in the dorsal and median raphe nuclei. The binding of the antagonist radioligand [3H]MPPF to 5-HT(1A) receptor sites was not altered, suggesting that the observed changes in 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding were not due to changes in receptor number. Thus, the desensitization of somatodendritic 5-HT(1A) autoreceptors in the dorsal and median raphe following chronic SSRI treatment appears to be due to a reduced capacity of the 5-HT(1A) receptor to activate G protein. By contrast, no significant change in postsynaptic 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding was observed in any of the forebrain areas examined following chronic antidepressant treatment. Thus, changes in postsynaptic 5-HT(1A) receptor-mediated responses reported to follow chronic SSRI or tricyclic antidepressant administration most likely occur distal to receptor-G protein interaction, perhaps at the level of effector, or involving changes in neuronal function at the system or circuit level.


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CRRD Object Information
CRRD ID: 2303632
Created: 2009-02-20
Species: All species
Last Modified: 2009-02-20
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.