The Effect of Unilateral Dopaminergic Deafferentation on Kainic acid Induced Seizures in the Rat

ABSTRACT

There has been quite a number of research regarding the role of dopamine in epilepsy and it has been still very controversial, In this study, the effect of dopaminergic deafferentation on kainic acid induced seizures was evaluated with behavioral study and molecular biologic method. We produced unilateral dopaminergic deafferentation via injection of 6-hydroxydopamine at the location of right substantia nigra in the Spague- Dawley rats (250-300gm) using the stereotaxic technique under pentobarbital anesthesia. Four weeks after this procedure, kainic acid (10m9/kg) was injected into the peritoneal cavity for induction of seizures. Observations of seizure pattern and mRNA expression of c-fos, dynorphin and enkephalin were obtained in the lesion group and were compared with those in the non-lesion group in terms of behavior characteristics and in situ hybridization histochemistry. In behavior study, the results demonstrated that more severe seizure patterns (rearing, falling, tonic-clonic seizure and status epilepticus) and more fast seizure evolution time(from onset to stage V) in the lesion group than those in the non-lesion group, which may indicated statistically significant (16.21+/-12.84 min. vs 35.88+/-16.55 min., p(0.05) The results of in situ hybridization revealed that the expression of c-fos, dynorphin and enkephalin mRNAs in certain areas of brain was higher in the lesion group than that in non-lesion group; c-fos in cerebral cortex, dynorphin in dentate gyrus, enkephalin in the entorhinal cortex and amygdala nuclei. Although the lesion was unilateral, the mRNA expression patterns appeared symmetrical shape. The characteristic behavior and molecular biologic study results are suggested that the dopamine may plays a important role in control of kainic acid induced seizures.