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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 vivo models,and associations with dopamine D2 receptors.Treatment with PGD at 1-5 g·L-1 significantly suppressed prolactin(PRL) secretion and synthesis in MMQ cells,a model of hyperPRL 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 somatolactotropic tumor-derived GH3 cells that lack the D2 receptor expression.In a rat model of hyper PRL,produced by repeated injection 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 dopamine D2 receptor agonist currently used for treatment of hyperPRL.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 receptors.The present study provides experimental evidence in support of clinical use of PGD as an effective treatment of antipsychotic-induced hyperPRL.