Abstracts

RATIONALE: We reported a characteristics of substantia nigra induced by a local injection of kainic acid(KA) into substantia nigra pars reticulata(SNr): Epilepsia 41(suppl 7):239, 2000. In order to clarify the relationship between epileptic excitation of SNr and local GABA concentration, GABA-A agonist(muscimol) was locally injected into unilateral SNr after induction of SN seizures by a kainic acid microinjection into SNr. Behavior, EEG, local cerebral glucose utilization(LCGU) and local benzodiazepine receptor binding(¹²⁵I-Iomazenil) were studied.
METHODS: (1) Experiment 1: Sixteen Wistar rats were used. Under intraperitoneal pentobarbital anesthesia, a stainless-steel cannula was inserted stereotaxically into the left SNr for KA injection. For EEG recording, a depth electrode was inserted into the left SNr, just posterior to the tip of the injection guide cannula. At 7 days after surgery, 1microgram of KA was injected into the left SNr(8 rats) and followed by a 1.0 microgram(8 rats) of muscimol injection into the focus of SNr. Behavior of the rats and EEG were continuously recorded for about 30 hours, and intermittently monitored following 1 month by the use of a video EEG monitoring system.
(2)Experiment 2: About two hour after KA and muscimol injection, 100 mCi of [¹⁴C]2-deoxyglucose(2DG) was intravenously injected, and the rats were processed for autoradiographic study. In another 8 rats, after KA and muscimol treatment, ¹²⁵I-Iomazenil was intravenously injected, and the rats were processed for autoradiographic study.
RESULTS: (1) On EEG, a secondary generalized seizure status was observed at about 70 minutes after KA injection in control rats. Limbic seizure manifestations such as salivation were observed as a initial symptom and followed by rolling and generalized tonic seizures. In the muscimol group, a secondary generalized seizure status was observed at about 200 minutes after KA injection, however, rolling manifestation during seizure was suppressed.
(2) In ¹⁴C-deoxyglucose autoradiogram, increased LCGUs in the lateral septal nucleus, ventroposterior lateral nucleus of the thalamus, amygdala were observed. In ¹²⁵I-Iomazenil autoradiogram, increased bindings were observed in the globus pallidus, hippocampus, ventroposterior lateral nucleus of the thalamus, amygdala and ventral tegmental area.
CONCLUSIONS: Muscimol not only inhibited progression of SNr seizures but also reduced epileptic activities of SNr seizures. Increase of benzodiazepine receptor binding of SNr can activate the GABAergic projection system and may be possible to control the seizure activities.