Neurotransmitters involved in the Opioid Regulation of Prolactin Secretion at the end of Pregnancy in Rats

SOAJE M; BREGONZIO C; CARÓN RW; DEIS RP

NEUROENDOCRINOLOGY

KARGER

Lugar: Basel; Año: 2004 vol. 80 p. 11 - 20

0028-3835

Using a pharmacological approach, we explored potentialmechanisms for the regulation of prolactin secretionby opioid peptides at the end of pregnancy in rats. Onday 19 of pregnancy, intracereboventricular administrationof the Ì-opioid receptor agonist (D-Ala2, NMe-Phe4,Gly-ol5)-enkephalin (DAMGO) or ß-endorphin (ß-END) induceda dose-related increase in serum prolactin levels30 min later. Pretreatment with the opioid antagonist naloxoneabolished the increase induced by DAMGO injection.At lower doses, DAMGO and ß-END did not modifythe 3,4-dihydroxyphenylacetic acid/dopamine ratio, butat higher doses, the Ì-agonists evoked a significantincrease of the dopaminergic activity as compared withsaline control. The time course of the effects of ß-END(2.5 Ìg/rat) showed a higher increase in serum prolactinlevels at 15 min than at 30 min after treatment.The 3,4-dihydroxyphenylacetic acid/dopamine ratio increased15 min after ß-END administration and was evenhigher 30 min later. Neither the selective Î-agonistU50,488H nor the selective ?-agonist (D-Pen2, D-Pen5)-enkephalin were able to modify the serum prolactin levelsat the doses studied.To evaluate potential neurotransmittersinvolved in the regulation of prolactin secretionat the end of pregnancy, we combined the administrationof serotoninergic or GABAergic antagonists withthe opioid agonist DAMGO. The serotonin 5-HT2 receptorantagonist ketanserin increased the serum prolactinlevels and potentiated the effect of DAMGO. The intracerebroventricularadministration of SR-95531 did notmodify the serum prolactin concentration under basalconditions, but partially prevented the increase inducedby DAMGO injection. The intracerebroventricular administrationof the GABAB receptor antagonist phaclofenhad no effect on the serum prolactin levels either in naiveor DAMGO-treated rats. The present results support theproposal that activation of Ì-opioid receptors stimulatesprolactin secretion at the end of pregnancy. Although theexact mechanisms by which the opioid system modulatesprolactin secretion at the end of pregnancy areunclear, these results suggest an interaction of theopioidergic system with serotoninergic and GABAergicsystems, without ruling out a direct or indirect action ondopaminergic neurons. In conclusion, the opioid systemmay regulate prolactin secretion at the end of pregnancythrough either stimulatory (present results) or inhibitoryactions previously described.