Long-term fluoxetine, but not desipramine, inhibits the ACTH and oxytocin responses to the 5-HT1A agonist, 8-OH-DPAT, in male rats

Qian Li, Andrew D. Levy, Theresa M. Cabrera, Mark S. Brownfield, George Battaglia, Louis D. Van de Kar

Research output: Contribution to journalArticlepeer-review


The present studies determined whether serotonin 5-HT1A receptor-mediated function is modified by chronic exposure to antidepressants. Hormone responses to the 5-HT1A agonist, 8-OH-DPAT, were evaluated after long-term exposure to two antidepressants, the 5-HT uptake blocker, fluoxetine, and the norepinephrine uptake blocker, desipramine (DMI). In addition, the density and affinity of 5-HT1A receptors in the hypothalamus and cerebral cortex were measured. Male rats received fluoxetine (10 mg/kg i.p.), DMI (5 mg/kg i.p) or saline injections once daily for 21 days. 8-OH-DPAT (0-500 μg/kg s.c.) was administered 18 h after the final antidepressant injection and 15 min before sacrifice. 8-OH-DPAT significantly increased plasma ACTH, corticosterone, oxytocin and prolactin, but not renin or vasopressin concentrations. Chronic injections of fluoxetine inhibited the ACTH, corticosterone and oxytocin responses to 8-OH-DPAT. suggesting reduced 5-HT1A receptor function. In contrast, chronic DMI did not alter the hormone responses to 8-OH-DPAT. The density and affinity of 5-HT1A receptors in the frontal cortex or hypothalamus were not altered by either fluoxetine or DMI. To verify that the observed effects require prolonged exposure to fluoxetine, rats received a single injection of fluoxetin (10 mg/kg, i.p.), 3 h before 8-OH-DPAT (0-500 μg/kg s.c.). Acute fluoxetine did not reduce any of the hormone responses to 8-OH-DPAT. In conclusion, the results suggest that chronic, but not acute, exposure to fluoxetine decreases 5-HT1A receptor function. This effects is not seen in rats chronically exposed to DMI. The mechanism of the effects of chronic fluoxetine on 5-HT1A receptor-mediated hormone responses is not likely due to reduced density of 5-HT1A receptors, because no changes were observed in [3H]8-OH-DPAT binding in hypothalamus and cortex, but could be due to changes in signal transduction.

Original languageEnglish (US)
Pages (from-to)148-156
Number of pages9
JournalBrain research
Issue number1-2
StatePublished - Dec 10 1993
Externally publishedYes


  • Antidepressant
  • Corticosterone
  • Prolactin
  • Renin
  • Serotonin
  • Vasopressin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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