An investigation of serotonergic involvement in the regulation of ACTH and corticosterone in the olfactory bulbectomized rat

Pharmacol Biochem Behav. 1999 Aug;63(4):599-605. doi: 10.1016/s0091-3057(99)00024-6.


The bilateral olfactory bulbectomy resulted in significantly higher plasma concentration of corticosterone, but not of ACTH in basal conditions and much higher plasma ACTH and corticosterone concentrations after 15 min of immobilization stress than were observed in sham-operated animals. Daily treatment with fluoxetine-a specific serotonin reuptake inhibitor-(15 mg/kg/day) had no effect on basal ACTH and corticosterone concentrations in OB rats. Fluoxetine treatment caused lower levels of ACTH, but not of corticosterone secretion, in response to immobilization stress. Bulbectomy significantly reducing 5-HT concentration in the amygdala. Stress increased serotonergic activity in the hypothalamus but not in the amygdala of OB rats. Chronic fluoxetine treatment of both unstressed and stressed OB rats resulted in a lower turnover rate in the two structures. Our results suggest that the hypercorticosteronemia observed after bulbectomy in unstressed OB rats is independent of the serotonergic system in both hypothalamus and amygdala. In contrast, they also demonstrate hypothalamic 5-HT changes in the HPA hyperactivity of OB rats in response to stress. Chronic fluoxetine treatment may normalize pituitary ACTH secretion in response to stress, possibly desensitization of the 5-HT receptors in the hypothalamus due to 5-HT being move available at the synapses.

MeSH terms

  • Adrenocorticotropic Hormone / metabolism*
  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Chromatography, High Pressure Liquid
  • Corticosterone / metabolism*
  • Fluoxetine / pharmacology
  • Hydroxyindoleacetic Acid / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Male
  • Olfactory Bulb / physiology*
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / physiology*
  • Stress, Psychological / metabolism


  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Adrenocorticotropic Hormone
  • Corticosterone