IL-1beta increases norepinephrine level in rat frontal cortex: involvement of prostanoids, NO, and glutamate.
The effects of local administration of interleukin-1beta (IL-1beta) were studied by using an intracerebral microdialysis technique in rats. A local injection of IL-1beta (3 and 10 ng) induced an elevation of norepinephrine (NE) concentration in the medial prefrontal cortex (mPFC). IL-1-receptor antagonist (800 ng) completely blocked the IL-1beta-induced NE increase. Diclofenac, a cyclooxygenase inhibitor (500 microM), and Nomega-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor (100 microM), applied through the dialysis probe, did not affect the initial rise in NE levels observed 20 min after injection of IL-1beta but completely suppressed the late phase of IL-1beta-induced NE increase at 40 min and thereafter. In contrast, local perfusion of 6-cyno-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartic acid (NMDA) glutamate-receptor antagonist (50 microM), but not DL-2-amino-5-phosphonovaleric acid, an NMDA-receptor antagonist (100 microM), blocked both phases of IL-1beta-induced NE increase. Furthermore, a microinjection of IL-1beta elevated the extracellular concentration of glutamate in the mPFC. These findings suggest that the IL-1beta-induced rise in NE levels in the mPFC is caused by activation of the glutamatergic system and the glutamate-induced increases in prostanoids and NO.
Kamikawa
H
H
Department of Psychiatry, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Hori
T
T
Nakane
H
H
Aou
S
S
Tashiro
N
N
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005625:Frontal Lobe / Q000378:metabolism*; D018698:Glutamic Acid / Q000502:physiology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011453:Prostaglandins; D012795:Sialoglycoproteins; D004008:Diclofenac; D019335:Nitroarginine; D009569:Nitric Oxide; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D019001:Nitric Oxide Synthase; D009638:Norepinephrine