title: Mu and kappa opioid receptor expression in the mediobasal hypothalamus and effectiveness of selective antagonists on prolactin release during lactation.
abstract: Endogenous opioid peptides are involved in prolactin release during lactation, in part by decreasing tuberoinfundibular dopaminergic (TIDA) neuronal activity. Both mu (mu) and kappa (kappa) opioid receptors have a role in the suckling-induced prolactin rise after 4-5 h up deprivation. The aim of this study was to investigate effects of mu opioid receptor antagonist, beta-funaltrexamine (beta-FNA), and kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI), on prolactin secretion and TIDA neuronal activity in lactating rats after 18 h pup deprivation. After 4 h separation from pups, the suckling-induced prolactin rise was abolished by 16 microg nor-BNI and 5 microg beta-FNA, coincident with increased dihydroxyphenylacetic acid (DOPAC):dopamine ratio in the stalk-median eminence (SME). However, after 18 h pups separation, these same doses of nor-BNI and beta-FNA did not alter the prolactin surge or DOPAC:dopamine ratios in the SME. Higher doses of nor-BNI (32 microg) and beta-FNA (10 microg) were required to inhibit suckling-induced prolactin secretion. beta-FNA (10 microg) increased the DOPAC:dopamine ratio in the SME, whereas nor-BNI (32 microg) treatment had no effect. The mu and kappa opioid receptor mRNA levels in the mediobasal hypothalamus were similar to suckled control rats after 4 h pup deprivation, but increased 1.4-fold after 18 h pup deprivation. These data support involvement of endogenous opioidergic systems in the suckling-induced prolactin rise after a prolonged (18 h) period of pup deprivation, as well as the shorter (4 h) pup deprivation period previously reported. Suppression of TIDA neuronal activity likely played a part in mu opioid receptor input to the suckling-induced prolactin rise after both 4 h and 18 h separation, whereas non-dopaminergic input was implicated with kappa opioid receptors after 18 h pup deprivation. Increased mu and kappa opioid receptors gene expression in the mediobasal hypothalamus may contribute to reduced effectiveness of opioid receptor antagonists to block suckling-induced prolactin release after 18 h pup deprivation.
authors.affiliation: Department of Physiology, Mail Code 6523, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tavakoli-Nezhad
authors.forename: L A
authors.initials: LA
authors.lastname: Arbogast
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000833:Animals, Suckling; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D007276:Injections, Intraventricular; D007774:Lactation / Q000187:drug effects / Q000378:metabolism*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013391:Sucking Behavior / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; D011388:Prolactin; D004298:Dopamine