Effect of pentobarbital on postischemic MK-801, muscimol, and naloxone bindings in the gerbil brain

Abstract

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), γ-aminobutyric acid A (GABA A), 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 GABA A receptors are unaffected. They also demonstrate that opiate receptors are severe affected by the treatment of pentobarbital, compared with NMDA and GABA A receptors. These findings are of interest in relation to the mechanism of ischemic neuronal damage.