Neuroendocrine responses to the serotonin₂ agonist DOI are differentially modified by three 5-HT_1A agonists

Evidence suggests that activation of 5-HT_1A receptors leads to inhibition of 5-HT₂-mediated behavior. The purpose of this study was to investigate the interaction between 5-HT_1A and 5-HT₂ receptor-mediated hormone secretion. Rats were pretreated with the 5-HT_1A agonists buspirone (0, 0.5, 2.0 mg/kg, i.p.), 8-OH-DPAT (0, 0.05, 0.2 mg/kg, s.c.) or ipsapirone (0, 1.0, 2.5 mg/kg, i.p.), 45 min before decapitation. The 5-HT₂ agonist DOI was administered (0-10 mg/kg, i.p.) 15 min after injection of the 5-HT_1A agonists. The three 5-HT_1A agonists differentially altered the DOI-induced increase of concentrations of hormone in plasma. None of the three 5-HT_1A agonists influenced the basal levels of renin, ACTH and prolactin but 8-OH-DPAT and buspirone increased the basal level of corticosterone in plasma. Also, 8-OH-DPAT increased the effects of DOI on the concentration of ACTH in plasma but ipsapirone and buspirone did not. None of the 5-HT_1A agonists significantly affected DOI-induced increase of concentration of corticosterone in plasma. Buspirone and 8-OH-DPAT potentiated the effect of DOI on prolactin in plasma, but ipsapirone did not. Ipsapirone potentiated the effect of DOI on the concentration of renin in plasma but this effect was not observed in 8-OH-DPAT- and buspirone-pretreated rats. The results do not support the hypothesis for a functional interaction between 5-HT_1A and 5-HT₂ receptors, since the three 5-HT_1A agonists did not have the same influence on the hormonal effects of DOI.