Activation of tuberohypophysial dopamine neurons following intracerebroventricular administration of the selective kappa opioid receptor antagonist NOR-binaltorphimine.
The effect of the kappa opioid receptor antagonist nor-binaltorphimine (NOR-BNI) was examined on the activity of dopamine (DA) neurons comprising the nigrostriatal, mesolimbic, and tuberohypophysial systems in the male rat. DA neuronal activity was estimated by measuring: (1) the concentration of the DA metabolite 3,4-dihydroxyphenylacetic acid and, (2) the accumulation of 3,4-dihydroxyphenylalanine after administration of a decarboxylase inhibitor in brain (striatum, nucleus accumbens) and pituitary regions (intermediate lobe, neural lobe) containing terminals of these neurons. The intracerebroventricular administration of NOR-BNI produced a dose- and time-related increase in the activity of tuberohypophysial DA neurons, but failed to alter the activity of nigrostriatal or mesolimbic DA neurons. The ability of NOR-BNI to enhance the activity of tuberohypophysial DA neurons was blocked by the kappa opioid agonist U-50,488. These results indicate that NOR-BNI, acting on kappa opioid receptors, activates tuberohypophysial DA neurons projecting to the neural and intermediate lobes of the pituitary.
Manzanares
J
J
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Lookingland
K J
KJ
LaVigne
S D
SD
Moore
K E
KE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017473:Receptors, Opioid, kappa
D006834:Hydrazines; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D015102:3,4-Dihydroxyphenylacetic Acid; C051844:norbinaltorphimine; D009271:Naltrexone; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D004298:Dopamine