J Korean Neurol Assoc.  2000 Mar;18(2):192-198.

Blockade of the Subthalamo-nigral Pathway Prevents the Motor Component of Pilocarpine Induced Generalized Convulsive Seizure in Rats

• Choi JY
• Kim HS
• Kim YI
• Park SM
• Lee KS
• Kim BS

Abstract

BACKGROUND: The substantia nigra pars reticulata is a critical site for the control of epileptic seizures. The potentiation of the inhibitory gamma-amino butyric acid (GABA) ergic input from the striatum to the substantia nigra pars reticulata suppresses primary or secondary generalized seizures in rats. Recent data suggests that the projection from the subthala-mus to the substantia nigra pars reticulata plays a critical role in the control of some forms of epileptic seizures.
METHODS
We examined the possible involvement of the excitatory glutamatergic input from the subthalamic nucleus (STN) to the substantia nigra in pilocarpine-induced seizures by the direct injection of GABA receptor agonist (muscimol) and n-methyl- D-aspartate (NMDA) receptor antagonist (MK-801) into the substantia nigra pars reticularis (SNr) and the subthalamic nucleus respectively. Sprague-Dawley rats were classified into four groups depending on the pretreatment; the injection of saline (STN sham) or muscimol (STN) into the subthalamic nucleus, and the injection of saline (SNr sham) or MK-801 (SNr) into the substantia nigra. Seizure was induced by the intraperitoneal injection of pilocarpine (400 mg/kg). RESULTS: Mean seizure stages in the STN group (1.5 +/-0.5) and SNr group (1.3 +/-0.5) were significantly lower than STN sham group (4.8 +/-0.4) and SNr sham group (4.8 +/-0.4) (P <0.05). Electroencephlograms showed typical status epilepticus patterns in the sham operation group but only discrete ictal discharges with slowing and intermittent ictal spikes were shown in both STN and SNr group. Viable cell numbers in the CA1 and CA3 in STN and SNr groups were significantly higher than those of the sham group (P <0.05).
CONCLUSIONS
These results provide evidence for the role of subthalamo-nigral projections in the modulation of pilocarpine-induced seizures.

Keyword

Subthalamus; Substantia nigra; Seizure; Muscimol; MK-801; Pilocarpine Manuscript received October 13

MeSH Terms

Animals
Butyric Acid
Cell Count
D-Aspartic Acid
Dizocilpine Maleate
Epilepsy
GABA Agonists
Injections, Intraperitoneal
Muscimol
Pilocarpine*
Rats*
Rats, Sprague-Dawley
Seizures*
Status Epilepticus
Substantia Nigra
Subthalamic Nucleus
Subthalamus
Butyric Acid
D-Aspartic Acid
Dizocilpine Maleate
GABA Agonists
Muscimol
Pilocarpine