Involvement of opioid receptor subtypes in both stimulatory and inhibitory effects of the opioid peptides on prolactin secretion during pregnancy.

1. We have previously demonstrated the existence of a dual neuromodulatory regulation of prolactin secretion by the opioid system. In the present work, we evaluated the opioid receptor subtypes involved in both the stimulatory and the inhibitory regulation of prolactin secretion in pregnant rats. 2. Specific opioid agonists and antagonists were administered intracerebro ventricular (i.c.v.) to rats on day 3 and on day 19 pregnancy in rats of pretreated with mifepristone. Blood samples were obtained after decapitation at 12.00 and 18.00 h. Serum prolactin levels were measured by RIA. 3. The mu-selective agonist DAMGO and beta-endorphin caused a significant increase in serum prolactin secretion on day 3 of pregnancy, during the diurnal surge and intersurge period. Pretreatment with naloxone prevented the increase on prolactin levels induced by DAMGO. The administration of U-50,488, a kappa-selective agonist or DPDPE, a delta-selective agonist, did not modify serum prolactin concentration while the mu1-antagonist naloxonazine reduced significantly serum prolactin levels. On day 19 of pregnancy, the release of prolactin induced by mifepristone was significantly increase by naloxonazine, while the kappa-antagonist nor-binaltorfimine induced only a small but significant increase. No effect was observed after administration of the delta-antagonist naltrindole. 4. We conclude that the mu-opioid receptor seems to be more specifically involved in both the stimulatory and inhibitory regulation by the opioid system on prolactin secretion during pregnancy. The increase on serum prolactin levels on day 3 after administration of DAMGO and beta-endorphin may suggest the participation of other regulatory mechanisms as the dopaminergic and serotoninergic systems. On day 19, only the endogenous ligands delta did not participate in the regulation of prolactin secretion, while the participation of the kappa-opioid receptor was significantly less effective than the endogenous ligand mu. Our results provide evidences of an important role of the opioid system through specific receptors on the regulation of prolactin secretion during early and late pregnancy.