Effect of selective serotonin receptor agonists on prolactin secretion in male rats

The effect of different serotonin (5-HT) receptor agonists on the release of prolactin (PRL) was investigated in conscious male rats. The 5-HT1 receptor agonists 5-carboxamidotryptamine and RU 24969 stimulated the PRL secretion dose dependently. RU 24969 possessed almost the same potency and efficacy (maximal effect) as 5-HT, while 5-carboxamidotryptamine was more potent and had a higher efficacy. The 5-HT1 + 2 receptor agonist MK 212 stimulated the PRL secretion only at high doses. The 5-HT2 receptor agonist S(alpha)methyl-5-HT and the 5-HT3 receptor agonist 2-methyl-5-HT had minor or no effect on the PRL secretion. The PRL-releasing effect of submaximal doses of 5-carboxamidotryptamine and RU 24969 was blocked by the 5-HT1 + 2 receptor antagonist methysergide and enhanced by other 5-HT agonists, but was unaffected by the 5-HT2 and 5-HT3 receptor antagonists. MK 212, S(alpha)methyl-5-HT, and--in particular--2-methyl-5-HT potentiated the effect of 5-carboxamidotryptamine. Likewise, 2-methyl-5-HT potentiated the effect of RU 24969, while MK 212 or S(alpha)methyl-5-HT had an additive to slightly potentiating effect. The findings show that 5-HT stimulates PRL secretion via 5-HT1 as well as 5-HT2 receptors and that activation of 5-HT2 and 5-HT3 receptors significantly augment the PRL-stimulating effect of 5-HT1 receptor activation. This indicates that the 5-HT receptor subtypes may interact functionally in the mediation of the PRL-releasing effect of the serotonergic system.