Serotonin-1A receptor function in the dorsal raphe nucleus following chronic administration of the selective serotonin reuptake inhibitor sertraline
Article first published online: 21 DEC 2007
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 105, Issue 4, pages 1091–1099, May 2008
How to Cite
Rossi, D. V., Burke, T. F., McCasland, M. and Hensler, J. G. (2008), Serotonin-1A receptor function in the dorsal raphe nucleus following chronic administration of the selective serotonin reuptake inhibitor sertraline. Journal of Neurochemistry, 105: 1091–1099. doi: 10.1111/j.1471-4159.2007.05201.x
- Issue published online: 21 DEC 2007
- Article first published online: 21 DEC 2007
- Received September 26, 2007; revised manuscript received December 4, 2007; accepted December 15, 2007.
- [35S]GTPγS binding;
- in vivo microdialysis;
- quantitative autoradiography;
- serotonin transporter binding
Serotonin-1A (5-HT1A) receptors in the dorsal raphe nucleus (DRN) function as somatodendritic autoreceptors, and therefore play a critical role in controlling serotonergic cell firing and serotonergic neurotransmission. We hypothesized that a decrease in the capacity of 5-HT1A receptors to activate G proteins was a general mechanism by which 5-HT1A receptors in the DRN are desensitized following chronic administration of selective serotonin reuptake inhibitors (SSRIs). Using in vivo microdialysis, we found that the ability of the 5-HT1A receptor agonist 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) (0.025 mg/kg, s.c.) to decrease extracellular 5-HT levels in striatum was attenuated following chronic treatment of rats with the SSRIs sertraline or fluoxetine. This apparent desensitization of somatodendritic 5-HT1A autoreceptor function was not accompanied by a decrease in 5-HT1A receptor sites in the coupled, high-affinity agonist state as measured by the binding of [3H]8-OH-DPAT. In marked contrast to what was observed following chronic administration of fluoxetine, 5-HT1A receptor-stimulated [35S]GTPγS binding in the DRN was not altered following chronic sertraline treatment. Thus, desensitization of 5-HT1A somatodendritic autoreceptor function following chronic sertraline administration appears not to be due to a decrease in the capacity 5-HT1A receptors to activate G proteins in the DRN. Our findings suggest that the SSRIs may not be a homogeneous class of antidepressant drug with regard to the mechanism by which the function of somatodendritic 5-HT1A autoreceptors is regulated.