Pharmacological activation of gamma-aminobutyric acid-system blunts prolactin response to mechanical breast stimulation in puerperal women.

To evaluate whether the gamma-aminobutyric acid (GABA)ergic system participates in the control of PRL secretion during the puerperium, different doses of sodium valproate (DPA), a drug that increases endogenous GABA activity, were administered orally to puerperal women who did not wish to breast feed their infants. Two groups of five women were each given DPA in doses of 400 and 800 mg, respectively. PRL levels were measured in plasma samples collected before and after drug administration. Another group of five puerperal women was treated with 800 mg DPA 60 min before mechanical breast stimulation using an electric breast pump for 15 min. Circulating PRL levels were measured in samples obtained before, during, and after breast stimulation. No drug-associated side effects were observed. After placebo administration, no significant variations in plasma PRL levels occurred in any subject. The lower dose of DPA (400 mg) induced a slight decrease in plasma PRL levels, but 800 mg of the drug induced a significant fall (P less than 0.05 vs. baseline values) in PRL, with a maximum percent decrease (68.2 +/- 4%) 180 min after DPA treatment. Mechanical breast stimulation performed after placebo treatment induced a significant increase (P less than 0.01) in plasma PRL levels, with peak values (37 +/- 10% above baseline values) 10 min after the onset of stimulation. When DPA was administered to the same women, a significant decrease (23 +/- 3%) in plasma PRL occurred during breast stimulation. Thereafter, PRL values continued to fall in spite of breast stimulation. PRL levels were significantly decreased after DPA treatment compared to both basal values (P less than 0.01) and the levels found in the same patients during control tests (P less than 0.05). These results demonstrate that enhancement of endogenous GABAergic tone induced by DPA significantly decreases basal PRL levels and blunts PRL release after mechanical breast stimulation. In agreement with animal data, a possible physiological role of GABA in the control of PRL release during puerperium may be suggested.