Effects of the selective dopaminergic D2 agonist quinelorane on the activity of dopaminergic and noradrenergic neurons projecting to the diencephalon of the rat.
The purpose of the present study was to characterize dopaminergic D2 receptor-mediated regulation of catecholaminergic neurons in the diencephalon by examining the acute effects of the potent and selective D2 agonist quinelorane (LY163502; trans-(-)-5,5a,6,7,8,9,9a,10-octahydro-6-propylpyrimido [4,5-g] quinolin-2-amine dihydrochloride dihydrate) on concentrations of 3,4-dihydroxyphenylacetic acid, dopamine, 3-methoxy-4-hydroxyphenylethyleneglycol and norepinephrine in the dorsomedial nucleus of the hypothalamus and horizontal limb of the diagonal band of Broca of intact and norepinephrine-depleted male rats. For comparative purposes, various other diencephalic brain regions and the nucleus accumbens were also examined. The results of this study reveal that quinelorane decreases the activity of dopaminergic neurons in the nucleus accumbens, horizontal limb of the diagonal band of Broca and dorsomedial nucleus of the hypothalamus, whereas it increases the activity of noradrenergic neurons projecting to the dorsomedial nucleus of the hypothalamus, but not the horizontal limb of the diagonal band of Broca. These inhibitory and stimulatory actions of quinelorane are blocked by or reverse the effects of the D2-selective antagonist raclopride, indicating that quinelorane is acting at D2 receptors. Taken together, these results indicate that quinelorane inhibits DA neurons within the diencephalon, whereas it activates a subpopulation of noradrenergic neurons projecting to this brain region.
Eaton
M J
MJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
Lookingland
K J
KJ
Moore
K E
KE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D004027:Diencephalon / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000032:analysis; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects*
D015259:Dopamine Agents; D011804:Quinolines; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D004298:Dopamine; D009638:Norepinephrine; C047726:quinelorane