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

1993; Elsevier BV; Volume: 630; Issue: 1-2 Linguagem: Inglês

10.1016/0006-8993(93)90652-4

1872-6240

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

Maternal Mental Health During Pregnancy and Postpartum

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.