Developmental and Regional Alteration of [kappa]-Opioid Receptors in Seizure-Susceptible EL Mouse Brain

The binding of [^sup 3^H]ethylketocyclazocine ([^sup 3^H]EKC) under the suppression of μ and δ sites in the brain of EL mice (seizure-susceptible) was examined to determine the relationship between seizures and the dynorphinergic system. The density of κ-opioid receptors in the cerebrum of adult EL mice during interictal periods significantly increased, without changes in apparent affinities, compared with that of adult ddY mice (seizure-nonsusceptible; the mother strain of EL). Subsequently, the binding of 0.8 nM [^sup 3^H]EKC in 8 brain regions was examined in the 2 strains. The [^sup 3^H]EKC binding in 25-day-old EL mice that had no seizures significantly increased in the hippocampus and amygdala. At the age of 50 days, EL mice displayed abortive seizures, and the number of κ sites in EL mice was significantly greater in the hippocampus, amygdala and cerebral cortex. It was further shown that the binding of [^sup 3^H]EKC in 150-day-old adult EL mice during interictal periods was markedly increased in the hippocampus, amygdala, cerebral cortex and striatum, compared with the corresponding regions in ddY mice. The up-regulation of κ receptors in the EL mouse brain may result from deficits in endogenous dynorphins, which could be involved in the pathogenesis of seizure diathesis and seizure manifestations in the EL mouse.[PUBLICATION ABSTRACT]