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Abstract: 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 prolactin (PRL) secretion using in vitro and in vivo models, with specific attention to the role of dopaminergic mediators and other sex hormones. Treatment with PGD at 1–5mg/ml significantly suppressed 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 10μM haloperidol, a dopamine D2 receptor antagonist. Consistent with a D2-action, PGD did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression but significantly increased the expression of D2 receptors and dopamine transporters (DAT) in PC12 cells. In a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide (MCP), chronic PGD (2.5–10g/kg daily) significantly reduced elevated serum PRL. The reduction in magnitude was similar to that elicited by bromocriptine (BMT), a 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 not only with D2 receptor and DAT modulation, but also with a normalization of other sex hormone dysfunction. This experimental evidence supports clinical use of PGD as an effective treatment of antipsychotic-induced hyperPRL. [Copyright &y& Elsevier]

Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D 2 receptor (DRD 2 ) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5–10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD 2 , DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD 2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD 2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL. [ABSTRACT FROM AUTHOR]