Effects of 8-OH-DPAT on corticosterone after acute and chronic administration of antidepressants

1. Serotonin has a facilitary role in the role of corticosterone secretion. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A agonist, dose dependently (0.25- 1.0 mg/kg i.p.) increased rat plasma corticosterone concentration. 2. 3 days parachlorophenylalanine (PCPA) (150 mg/kg) administration did not effect the 8-OH-DPAT-induced corticosterone secretion. 3. Corticosterone responses to 8-OH-DPAT (0.5 mg/kg) were significantly attenuated by pretreatment with propranolol (5 mg/kg). Ketanserin (2 mg/kg), haloperidol (0.2 mg/kg), prazosin (0.1 mg/kg), and ICS-205930 (30 mu/kg) failed to antagonize the corticosterone response to 8-OH-DPAT. 4. 8-OH-DPAT-induced corticosterone were investigated in male rats after treatment with mianserin (2, 10 mg/kg), imipramine (5 mg/kg), desipramine (5 mg/kg), doxepine (5 mg/kg) for 1 day or 3 weeks. Chronic mianserin (10 mg/kg) and doxepine (5 mg/kg) did significantly increase 8-OH-DPAT-induced corticosterone response. Acute antidepressant, chronic imipramine, desipramine and mianserin (2 mg/kg) treatment did not change it. 5. These findings demonstrate that chronic treatment of some antidepressants potentiates 8-OH-DPAT-induced increase in plasma corticosterone, by actions at 5-HT-1A receptors located postsynaptically on 5-HT neurones.