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 striaturn 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-mu-M)-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 H-3-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-fluoromethythistidine, 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.