Neurotransmitters involved in the opioid regulation of prolactin secretion at the end of pregnancy in rats.
Using a pharmacological approach, we explored potential mechanisms for the regulation of prolactin secretion by opioid peptides at the end of pregnancy in rats. On day 19 of pregnancy, intracereboventricular administration of the mu-opioid receptor agonist (D-Ala2, NMe-Phe4, Gly-ol5)-enkephalin (DAMGO) or beta-endorphin (beta-END) induced a dose-related increase in serum prolactin levels 30 min later. Pretreatment with the opioid antagonist naloxone abolished the increase induced by DAMGO injection. At lower doses, DAMGO and beta-END did not modify the 3,4-dihydroxyphenylacetic acid/dopamine ratio, but at higher doses, the mu-agonists evoked a significant increase of the dopaminergic activity as compared with saline control. The time course of the effects of beta-END (2.5 microg/rat) showed a higher increase in serum prolactin levels at 15 min than at 30 min after treatment. The 3,4-dihydroxyphenylacetic acid/dopamine ratio increased 15 min after beta-END administration and was even higher 30 min later. Neither the selective kappa-agonist U50,488H nor the selective delta-agonist (D-Pen2, D-Pen5)- enkephalin were able to modify the serum prolactin levels at the doses studied. To evaluate potential neurotransmitters involved in the regulation of prolactin secretion at the end of pregnancy, we combined the administration of serotoninergic or GABAergic antagonists with the opioid agonist DAMGO. The serotonin 5-HT2 receptor antagonist ketanserin increased the serum prolactin levels and potentiated the effect of DAMGO. The intracerebroventricular administration of SR-95531 did not modify the serum prolactin concentration under basal conditions, but partially prevented the increase induced by DAMGO injection. The intracerebroventricular administration of the GABA(B) receptor antagonist phaclofen had no effect on the serum prolactin levels either in naive or DAMGO-treated rats. The present results support the proposal that activation of mu-opioid receptors stimulates prolactin secretion at the end of pregnancy. Although the exact mechanisms by which the opioid system modulates prolactin secretion at the end of pregnancy are unclear, these results suggest an interaction of the opioidergic system with serotoninergic and GABAergic systems, without ruling out a direct or indirect action on dopaminergic neurons. In conclusion, the opioid system may regulate prolactin secretion at the end of pregnancy through either stimulatory (present results) or inhibitory actions previously described.
Soaje
Marta
M
Laboratorio de Reproducción y Lactancia, IMBECU-CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina. msoaje@lab.cricyt.edu.ar
Bregonzio
Claudia
C
Carón
Rubén W
RW
Deis
Ricardo P
RP
D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000008:administration & dosage; D005260:Female; D018756:GABA Antagonists / Q000008:administration & dosage; D007276:Injections, Intraventricular; D009294:Narcotics / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011388:Prolactin / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage; D001615:beta-Endorphin / Q000008:administration & dosage
D000701:Analgesics, Opioid; D018756:GABA Antagonists; D009294:Narcotics; D018377:Neurotransmitter Agents; D017450:Receptors, Opioid, mu; D012702:Serotonin Antagonists; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001615:beta-Endorphin; D011388:Prolactin; D004298:Dopamine