Non-NMDA receptor-mediated regulation of hypothalamic dopaminergic neurons in the rat.
The purpose of the present study was to examine the effects of non-NMDA receptor blockade and activation on the activity of tuberoinfundibular dopaminergic (TIDA), periventricular-hypophysial dopaminergic (PHDA) and, for comparison, nigrostriatal dopaminergic (NSDA) neurons in male and female rats. The activity of TIDA, PHDA and NSDA neurons was estimated by measuring the concentration of the primary dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence, intermediate lobe of the posterior pituitary and striatum, respectively. Systemic administration of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-selective antagonist 6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3(1H,4H)-dione (NBQX) increased DOPAC concentrations in the median eminence and intermediate lobe, and decreased plasma concentrations of prolactin and alpha-MSH, in a dose- and time-related manner. In contrast, NBQX had no effect on DOPAC concentrations in the striatum, suggesting that non-NMDA receptors are not involved in the tonic regulation of NSDA neurons. The increase in DOPAC concentrations in the median eminence and intermediate lobe, and the decrease in plasma concentrations of prolactin and alpha-MSH, produced by NBQX were prevented by AMPA but not by kainic acid. Taken together, the results demonstrate that endogenous excitatory amino acid neurotransmitters, acting at AMPA receptors, tonically inhibit both TIDA and PHDA neurons, and thereby increase the secretion of prolactin and alpha-MSH in male and female rats.
Wagner
E J
EJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Moore
K E
KE
Lookingland
K J
KJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011388:Prolactin / Q000097:blood; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017459:Receptors, Amino Acid / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D000521:alpha-MSH / Q000097:blood
D011810:Quinoxalines; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D015102:3,4-Dihydroxyphenylacetic Acid; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D000521:alpha-MSH; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011388:Prolactin; D007608:Kainic Acid; D004298:Dopamine