Inhibition of suckling-induced prolactin release by mu- and kappa-opioid antagonists.
Evidence suggests that endogenous opioid peptides (EOP) are involved in the hyperprolactinemia and suppression of luteinizing hormone (LH) release associated with lactation. To address this hypothesis, we investigated the effects of various opioid receptor antagonists on suckling-induced prolactin (PRL) and LH responses in primiparous, lactating rats. All animals were fitted with indwelling jugular catheters to allow serial blood sampling, and some rats received intracerebroventricular (i.c.v.) cannulae for central drug injection. Naloxone (2.0 mg/kg, i.v.) was employed as a broad spectrum opioid antagonist, whereas beta-funaltrexamine (beta-FNA, 1.0-5.0 micrograms, i.c.v.), naloxonazine (NAZ, 20 mg/kg, i.v.) and nor-binaltorphimine (nor-BNI, 4.0-16.0 micrograms, i.c.v.) were used to block mu, mu 1 and kappa receptor sites, respectively. In vehicle-treated rats, pup suckling evoked a dramatic increase in plasma PRL and a concurrent decrease in circulating LH. Naloxone caused a modest, though significant, attenuation of the PRL surge during nursing. beta-FNA and nor-BNI inhibited suckling-induced PRL release in a dose-related fashion, and at sufficient doses, both antagonists abolished the PRL response. Conversely, the suckling-induced rise in plasma PRL was not affected by NAZ. Naloxone, beta-FNA, and NAZ did not alter the profile of circulating LH in suckled rats, but the highest dose nor-BNI (16 micrograms, i.c.v.) produced a significant elevation in plasma LH. However, even in rats treated with 16.0 micrograms of nor-BNI, plasma LH levels declined in response to the nursing stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
Baumann
M H
MH
Department of Biological Sciences, Rutgers University, Piscataway, NJ 08855.
Rabii
J
J
D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D007774:Lactation / Q000187:drug effects / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011388:Prolactin / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; C034643:naloxonazine; D011388:Prolactin; D007986:Luteinizing Hormone