Mechanisms for the stimulatory effects of opioidergic and serotonergic input signals on prolactin in pregnant rats.

Dopamine (DA) neurons participate in tonic inhibition of prolactin (PRL), whereas beta-endorphin (beta-End) and serotonin (5-HT) neurons appear to be important stimulatory links for nocturnal PRL surges that occur throughout the first half of pregnancy in the rat. The purpose of this study was to determine how these neuronal components might be organized within the pathway controlling PRL release during gestation. Maximal stimulation of DA receptors with the agonist bromocriptine mesylate (Bromo) completely blocked the PRL response to beta-End (100 ng/microliters/min for 15 min) given intracerebroventricularly (i.c.v.) on day 8 of pregnancy. DA receptor blockade, produced by implanting a 25 mg pellet of haloperidol (Hal) on day 7 of pregnancy, resulted in PRL levels of 500-600 ng/ml by the following morning. beta-End i.c.v. or 250 mg/ml/kg BW of the DA synthesis inhibitor, alpha-methyl-p-tyrosine (alpha-MPT), given during the intersurge period, were equally effective in significantly increasing PRL (p less than 0.01) above pretreatment levels. beta-End and alpha-MPT evoked similar increases in rats pretreated with Hal, suggesting the stimulatory effect of beta-End on nocturnal PRL surges may primarily be due to DA inhibition. The next objective was to determine how beta-End and 5-HT might interact to stimulate the nocturnal surge. Day 8 pregnant rats were infused continuously with the opioid receptor blocker, naloxone hydrochloride (Nal), at a rate of 2.0 mg/10 min from 1000-1300 h. The PRL response to an injection of 20 mg/kg BW 5-hydroxytryptophan (5-HTP) at 1200 h was greatly attenuated, compared to controls infused with saline instead of Nal. This suggests that 5-HT stimulates PRL, at least in part, by an action at opioid receptors. Distilled H2O or 10 mg/kg BW of the selective S2 receptor blocker, ketanserin tartrate (Ket), was given intraperitoneally (i.p.) during the intersurge period on day 8 of pregnancy. All animals demonstrated an identical response to beta-End given 2 hours later, regardless of the type of pretreatment. It appears that beta-End does not stimulate PRL by way of an S2 receptor. Although beta-End induced a significant increase in PRL on day 16 of pregnancy, the response was attenuated by more than 60% compared to the response on day 8 of pregnancy. This attenuation may involve placental lactogens, shown to be secreted during this time and to inhibit PRL secretion.(ABSTRACT TRUNCATED AT 400 WORDS)