Intravenously and iontophoretically administered naloxone reverses ischemic changes in rat hippocampus.
Forty rats under urethane anesthesia were subjected to cerebral ischemia by ligation of the right carotid, the right plus the left carotid, or the right carotid plus two vertebral arteries. Ischemia caused three types of changes in the field potential of the right hippocampal CA1 region evoked by fimbrial stimulation: 1) completely reversible deterioration (57% and 16% of the rats with unilateral and bilateral carotid artery ligation, respectively), 2) moderate deterioration (37% and 24% of the rats with unilateral and bilateral carotid artery ligation) and 3) irreversible loss of the evoked activity (6% and 60% of the rats with unilateral and bilateral carotid artery ligation and all the rats subjected to three-vessel occlusion). Naloxone improved the moderate deterioration in 10 of 11 rats (1-3 mg/kg i.v.) and in 15 of 16 (50-150 nA) iontophoretic applications, but naloxone did not restore the lost evoked activity. Intravenous morphine (10 mg/kg) aggravated the ischemic changes, and this effect was reversed by naloxone, while iontophoretic administration of morphine caused only excitation. These findings suggest that naloxone has a favorable effect on cerebral ischemia not severe enough to cause transmission failure. The reversal of ischemic changes by iontophoretic naloxone indicates that its site of action is at the neuronal or microcirculatory level.
Dalkara
T
T
Department of Neurology, Hacettepe University Hospitals, Ankara, Turkey.
Namer
I J
IJ
Onur
R
R
Zileli
T
T
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D004558:Electric Stimulation; D005071:Evoked Potentials; D006624:Hippocampus / Q000503:physiopathology*; D007478:Iontophoresis; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009270:Naloxone / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects
D009270:Naloxone; D009020:Morphine