Effect of pentobarbital on postischemic MK-801, muscimol, and naloxone bindings in the gerbil brain.
We investigated the postischemic alterations in [3H]MK-801, [3H]muscimol, and [3H]naloxone binding in the gerbil brain, and examined the effect of pentobarbital against these alterations. [3H]MK-801, [3H]muscimol, and [3H]naloxone were used to label N-methyl-D-aspartate (NMDA), gamma-aminobutyric acidA (GABAA), and opiate receptors, respectively. Transient cerebral ischemia was induced for 10 min, and pentobarbital (40 mg/kg) was administered intraperitoneally 30 min before ischemia. Five hours after ischemia, no conspicuous alteration in [3H]MK-801, [3H]muscimol, and [3H]naloxone binding was found in the striatum and hippocampus. Seven days after ischemia, [3H]MK-801 and [3H]naloxone binding was significantly decreased in the striatum and hippocampal area where histological neuronal damage was noted. By contrast, no significant change in [3H]muscimol binding was seen in the above regions except for the hippocampal CA3 sector. The treatment of pentobarbital caused a significant alteration in the binding of [3H]naloxone and [3H]muscimol in various brain areas 5 h after ischemia. However, this drug showed no significant change in [3H]MK-801 binding in the brain. Seven days after ischemia, pentobarbital partly ameliorated a significant reduction in [3H]MK-801 and [3H]naloxone binding in the striatum and hippocampus. A histological study also showed that pentobarbital afforded neuronal protection against the damage to the brain except for the hippocampal CA1 sector 7 days after ischemia. These results suggest that NMDA and opiate receptors are damaged after ischemia, whereas GABAA receptors are unaffected. They also demonstrate that opiate receptors are severe affected by the treatment of pentobarbital, compared with NMDA and GABAA receptors. These findings are of interest in relation to the mechanism of ischemic neuronal damage.
Kanai
Y
Y
Pharmacological Research Laboratory, Tokyo Tanabe Co. Ltd., Japan.
Araki
T
T
Kato
H
H
Kogure
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D010424:Pentobarbital / Q000494:pharmacology*; D011869:Radioligand Assay
D009118:Muscimol; D009270:Naloxone; D016291:Dizocilpine Maleate; D010424:Pentobarbital