Clinical studies have demonstrated the effectiveness of an herbal preparation called Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL).In the present study, we further examined the pharmacological action of PGD on hyperPRL in in vitro and in vi vo models, and associations with dopamine D2 receptors.Treat ment with PGD at 1-5 g· L-1 significantly suppressed prolactin (PRL) secretion and synthesis in MMQ cells, a model of hyper PRL derived from pituitary adenoma cells.The suppressive effects were completely abolished by pretreatment with 10 μmol·L-1 haloperidol, a dopamine D2 receptor antagonist.Consistent with a D2-action, PGD did not affect PRL in rat pituitary somato lactotropic tumor-derived GH3 cells that lack the D2 receptor ex pression.In a rat model of hyper PRL, produced by repeated in jection of metoclopramide (MCP) , another dopamine D2 receptor antagonist, chronic PGD (2.5-10 g· kg-1 daily) significantly reduced elevated serum PRL.The reduction in magnitude was similar to that elicited by bromocriptine (BMT), a potent dopa mine D2 receptor agonist currently used for treatment of hyper PRL.Neither PGD nor BMT altered serum estradiol, but PGD reversed decreased serum progesterone to control level, whereas BMT did not.These results indicate that the anti-hyperPRL effects of PGD are associated with the modulation of D2 recep tors.The present study provides experimental evidence in sup port of clinical use of PGD as an effective treatment of antipsy chotic-induced hyperPRL.