Abstract
Changes in 5-HT1A 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-HT1A receptor-stimulated [35S]GTPγS 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-HT1A receptor-stimulated [35S]GTPγS binding in the dorsal and median raphe nuclei. The binding of the antagonist radioligand [3H]MPPF to 5-HT1A receptor sites was not altered, suggesting that the observed changes in 5-HT1A receptor-stimulated [35S]GTPγS binding were not due to changes in receptor number. Thus, the desensitization of somatodendritic 5-HT1A autoreceptors in the dorsal and median raphe following chronic SSRI treatment appears to be due to a reduced capacity of the 5-HT1A receptor to activate G protein. By contrast, no significant change in postsynaptic 5-HT1A receptor-stimulated [35S]GTPγS binding was observed in any of the forebrain areas examined following chronic antidepressant treatment. Thus, changes in postsynaptic 5-HT1A 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.
Original language | English (US) |
---|---|
Pages (from-to) | 565-573 |
Number of pages | 9 |
Journal | Neuropsychopharmacology |
Volume | 26 |
Issue number | 5 |
DOIs | |
State | Published - 2002 |
Keywords
- 5-HT receptor
- 8-OH-DPAT
- Amitriptyline
- Fluoxetine
- Quantitative autoradiography
- [H]MPPF
- [S]GTPgammaS
ASJC Scopus subject areas
- Pharmacology
- Psychiatry and Mental health