Direct evidence for increased continuous histamine release in the striatum of conscious freely moving rats produced by middle cerebral artery occlusion.
Extracellular histamine in the stratum of conscious freely moving rats collected by intracerebral microdialysis 1 day after implantation of a U-shaped dialysis probe was measured by HPLC coupled with postcolumn o-phthalaldehyde derivatization fluorometry. The basal fractional histamine outputs were almost constant from 1 to 7 h after the start of perfusion (5.9-8.4 pg/30 min). Depolarization by perfusion with a high K+ (100 mM)-containing medium produced a significant (124%) increase and neuronal blockade by perfusion with a tetrodotoxin (1 microM)-containing medium resulted in a 68% reduction in the histamine output. The histamine output was markedly reduced by intraperitoneal injection of alpha-fluoromethylhistidine (100 mg/kg), an irreversible inhibitor of histidine decarboxylase, or (R)-alpha-methylhistamine (5 mg/kg), a potent and specific H3-receptor agonist. After middle cerebral artery (MCA) occlusion, the histamine output gradually increased, and reached four times the control value 8 h later. When rats were pretreated with metoprine (10 mg/kg), a histamine N-methyltransferase inhibitor, there was no significant difference in the histamine output between the MCA-occluded and the sham-operated groups during the first 3.5 h after the operation, but the histamine output gradually increased thereafter in the MCA-occluded group. In rats treated with alpha-fluoromethylhistidine, MCA occlusion failed to cause an increase in the histamine output. These results demonstrate that MCA occlusion induces a long-lasting increase in neuronal histamine release in the rat striatum.
Adachi
N
N
Department of Pharmacology, Okayama University Medical School, Japan.
Itoh
Y
Y
Oishi
R
R
Saeki
K
K
D000818:Animals; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D002544:Cerebral Infarction / Q000209:etiology; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D006632:Histamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011189:Potassium Chloride; C054284:alpha-fluoromethylhistamine; D006632:Histamine