Effects of the GABAergic drug, sodium valproate, on the prolactin release evoked by pharmacological stimuli in normal women.

Sodium valproate (DPA or Na-dipropylacetate), an anticonvulsant drug activating the endogenous GABAergic system, was administered orally at the dose of 400 mg to seventeen normal women 1 h before intravenous injections with three drugs which stimulate prolactin (PRL) release: TRH (200 micrograms bolus; six subjects); domperidone (5 mg bolus; six subjects); and sulpiride (5 mg bolus; five subjects). DPA pretreatment significantly blunted PRL response to both domperidone and sulpiride injections without affecting the PRL response to TRH. In particular, the quantitative PRL secretion (areas under curves) following domperidone and sulpiride tests appeared significantly reduced after DPA treatment in comparison to placebo (P less than 0.02 and P less than 0.01 for domperidone and sulpiride respectively). These results indicate that the pharmacological enhancement of the endogenous GABAergic system by DPA may blunt PRL response to both central and peripheral dopamine receptor blockade. These observations suggest that a GABAergic pathway inhibiting PRL secretion at the hypothalamic level competes, at least in part, with the dopaminergic system. Conversely, the lack of any effect of DPA on PRL response to TRH seems to suggest that pituitary TRH receptors are independent of any GABAergic control.