Neurochemical evidence that estrogen-induced suppression of kappa-opioid-receptor-mediated regulation of tuberoinfundibular dopaminergic neurons is prolactin-independent.
The purpose of the present study was to examine the role of estrogen and prolactin in determining the responsiveness of tuberoinfundibular dopaminergic (TIDA) neurons to kappa-opioid receptor blockade in female rats. TIDA neuronal activity was estimated by measuring either dopamine synthesis [accumulation of 3,4-dihydroxyphenylalanine (DOPA) 30 min after the administration of the decarboxylase inhibitor NSD-1015] or metabolism [concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC)] in terminals of these neurons in the median eminence. Blockade of kappa-opioid receptors with the selective kappa-antagonist norbinaltorphimine (NOR-BNI) increased the concentrations of DOPAC in the median eminence of ovariectomized rats but had no effect in gonadally intact rats, suggesting that loss of endogenous ovarian hormones following ovariectomy results in an increase in kappa-opioid-receptor-mediated inhibition of TIDA neurons. Estrogen administration ot ovariectomized rats blocked NOR-BNI-induced increases in median eminence DOPAC concentrations, whereas treatment of gonadally intact or ovariectomized, estrogen-treated rats with prolactin antiserum had no effect on the insensitivity of these neurons to NOR-BNI. Administration of antiserum to dynorphin A1-8 increased DOPA accumulation in the median eminence of ovariectomized but not estrogen-treated ovariectomized rats. Taken together, these results reveal that estrogen, acting via a prolactin-independent mechanism, suppresses kappa-opioid-receptor-mediated inhibition of the activity of TIDA neurons, possibly by decreasing the release of endogenous dynorphin.
Wagner
E J
EJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Manzanares
J
J
Moore
K E
KE
Lookingland
K J
KJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D004399:Dynorphins / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D007028:Hypothalamic Hormones / Q000494:pharmacology; D007276:Injections, Intraventricular; D008473:Median Eminence / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D010446:Peptide Fragments / Q000494:pharmacology; D011388:Prolactin / Q000502:physiology*; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000187:drug effects*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004967:Estrogens; D006834:Hydrazines; D007028:Hypothalamic Hormones; D010446:Peptide Fragments; D017473:Receptors, Opioid, kappa; D015102:3,4-Dihydroxyphenylacetic Acid; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; C026770:dynorphin (1-8); D011388:Prolactin; C004297:3-hydroxybenzylhydrazine; D004298:Dopamine