Serotonin-1A receptor function in the dorsal raphe nucleus following chronic administration of the selective serotonin reuptake inhibitor sertraline.

  • Rossi D
  • Burke T
  • McCasland M
 et al. 
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Serotonin-1A (5-HT(1A) 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-HT(1A) receptors to activate G proteins was a general mechanism by which 5-HT(1A) 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-HT(1A) 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-HT(1A) autoreceptor function was not accompanied by a decrease in 5-HT(1A) 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-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding in the DRN was not altered following chronic sertraline treatment. Thus, desensitization of 5-HT(1A) somatodendritic autoreceptor function following chronic sertraline administration appears not to be due to a decrease in the capacity 5-HT(1A) 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-HT(1A) autoreceptors is regulated.

Author-supplied keywords

  • 5-HT1A
  • Animals
  • Male
  • Raphe Nuclei
  • Rats
  • Receptor
  • Serotonin
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Sertraline
  • Sprague-Dawley
  • administration & dosage
  • drug effects
  • physiology

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  • Dania V Rossi

  • Teresa F Burke

  • Melissa McCasland

  • Julie G Hensler

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