Effects of immunoneutralization of dynorphin1-17 and dynorphin1-8 on the activity of central dopaminergic neurons in the male rat.
The effects of administration of antibodies against dynorphin1-17 (DYN1-17-AB) and dynorphin1-8 (DYN1-8-AB) were examined on the activity of dopaminergic (DA) neurons comprising the nigrostriatal, mesolimbic, tuberoinfundibular and periventricular-hypophysial systems in the male rat brain. DA neuronal activity was estimated by measuring the concentration of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in brain (striatum, nucleus accumbens, median eminence) and pituitary regions (intermediate lobe) containing terminals of these neurons. The intracerebroventricular administration of either DYN1-17-AB or DYN1-8-AB produced a time-related increase in the activity of tuberoinfundibular and periventricular-hypophysial DA neurons, but failed to alter the activity of nigrostriatal or mesolimbic DA neurons. The ability of both DYN1-17-AB and DYN1-8-AB to enhance the activity of tuberoinfundibular and periventricular-hypophysial DA neurons was reversed by the kappa opioid agonist U-50,488. These results indicate that DYN1-17-AB and DYN1-8-AB, presumably by binding endogenous dynorphins, remove a tonic inhibitory action of these opioid peptides on tuberoinfundibular and periventricular-hypophysial DA neurons.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
J
J
Manzanares
E J
EJ
Wagner
K J
KJ
Lookingland
K E
KE
Moore
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D004399:Dynorphins / Q000276:immunology*; D007276:Injections, Intraventricular; D008297:Male; D008473:Median Eminence / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010446:Peptide Fragments / Q000276:immunology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats
D000700:Analgesics; D010446:Peptide Fragments; D011759:Pyrrolidines; D015102:3,4-Dihydroxyphenylacetic Acid; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; C026770:dynorphin (1-8); D004298:Dopamine