Activation of melatonin receptor sites retarded the depletion of norepinephrine following inhibition of synthesis in the C3H/HeN mouse hypothalamus.
The aim of the present study was to determine the effect of activation of melatonin receptor sites on the activity of noradrenergic neurons in the C3H/HeN mouse brain. Changes in noradrenergic activity were assessed by measuring norepinephrine (NE) levels in the hypothalamus, frontal cortex, and hippocampus following inhibition of NE synthesis with alpha-methyl-p-tyrosine (alpha-MpT) (300 mg/kg, i.p., 2 h). 6-Chloromelatonin (1-30 mg/kg, i.p.) significantly retarded the alpha-MpT-induced decrease in NE levels in the hypothalamus, but not in hippocampus and frontal cortex. This effect was observed at 30 min and 60 min after 6-chloromelatonin administration and was dose dependent. At noon, when the levels of endogenous melatonin are low, the melatonin receptor antagonist luzindole (30 mg/kg, i.p., 30 min) did not affect the depletion of NE by alpha-MpT; however, it (1-30 mg/kg) completely antagonized the 6-chloromelatonin-induced reduction of NE depletion elicited by alpha-MpT in hypothalamus. These results suggest that activation of melatonin receptor sites in brain of C3H/HeN mouse retarded the depletion of NE elicited by alpha-MpT. At midnight, when the levels of melatonin are high, luzindole (30 mg/kg) significantly accelerated the depletion of NE by alpha-MpT in hypothalamus, but not in frontal cortex or hippocampus, suggesting activation of melatonin receptor sites by endogenous melatonin. We conclude that activation of melatonin receptor sites in C3H/HeN mouse brain by endogenous melatonin inhibits the activity of noradrenergic neurons innervating the hypothalamus.
Fang
J M
JM
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
Dubocovich
M L
ML
D000818:Animals; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D014018:Tissue Distribution; D014363:Tryptamines / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter; D014363:Tryptamines; C057154:luzindole; C024100:6-chloromelatonin; D019805:alpha-Methyltyrosine; D008550:Melatonin; D009638:Norepinephrine