Decreased Dopamine and Increased Norepinephrine Levels in the Spontaneously Epileptic Rat, a Double Mutant Rat

Abstract

Summary: Dopamine (DA) and norepinephrine (NE) brain levels and turnover rate were examined in the spontaneously epileptic rat (SER: zi/zi, tm/tm), a double mutant rat obtained by mating tremor heterozygotes (tml +) with zitter homozygotes associated with epileptic seizures composed of spontaneously occurring tonic convulsion and absence‐like seizure. DA and NE levels were also determined in age‐matched male zitter, tremor and Kyo:Wistar rats. DA levels in caudate nucleus were significantly lower in adult age (10–12 weeks) SER, which showed epileptic seizures, and zitter rats than in adultKyo:Wistar and tremor rats. DA levels in other areas such as thalamus‐hypothalamus, midbrain, and ponsmedulla were not different among SER, zitter, tremor, and Kyo:Wistar rats at age 10–12 weeks. Except in cerebral cortex and hippocampus, there were no differences in brain DA levels between young seizure‐free SER (age 5 weeks) and young Kyo:Wistar rats. Furthermore, the turnover rate of DA was significantly lower in caudate nucleus of adult SER than of Kyo:Wistar rat, whereas in pons‐medulla there was no difference between the two strains. In contrast, NE levels in the thalamushypothalamus, midbrain, cerebellum and pons‐medulla were higher in SER and zitter rats at age 10–12 weeks than in age‐matched tremor and Kyo:Wistar rats. Higher NE levels were also observed in midbrain, cerebellum, and pons‐medulla of young SER as compared with young Kyo:Wistar rats. Turnover rates of NE were significantly lower in pons‐medulla and cerebellum of the adult SER than in those of Kyo:Wistar rat. In genetic studies using backcross mating of zitter and BN rats, decreased DA was also observed in caudate nucleus of backcrossed zitter rats as compared with BN, F₁, and zitter wild‐type rats. Increased NE contents were observed in the thalamus‐hypothalamus, midbrain, and pons‐medulla of zitter rats as compared with other rats, although the increase was also observed in the thalamus‐hypothalamus and midbrain of zitter wild‐type rats. Results suggest that a decrease in DA in caudate nucleus and an increase in NE in midbrain and pons‐medulla are due to the homozygous zi gene, and together with previous findings, suggest that the decrease in DA, although probably not the only cause, facilitates appearance of tonic and absence‐like seizures by lowering the threshold triggering such seizures.