Regulation of seizure threshold by excitatory amino acids in the striatum and entopeduncular nucleus of rats.

The participation of excitatory neurotransmitter systems in the basal ganglia in the initiation and propagation of limbic seizures induced by pilocarpine has been investigated in the rat. Limbic seizures (electrographic and motor) occur in rats receiving bilateral microinjections into the entopeduncular nucleus of 12.5 nmol N-methyl-D-aspartate or 0.1 nmol kainate, 15 min prior to a subconvulsant dose of pilocarpine (150 mg/kg, intraperitoneally). N-Methyl-D-aspartate (12.5 nmol) or kainate (0.5 nmol), injected alone bilaterally into the entopeduncular nucleus, induce sniffing and grooming but no electrographic or behavioural seizures. Limbic seizures also occur after a subconvulsant dose of pilocarpine when it is preceded by injection of N-methyl-D-aspartate (12.5 nmol) or kainate (0.5 or 2 nmol) into the dorsal striatum. Behavioural and electrographic signs of limbic seizures following pilocarpine (380 mg/kg) are suppressed by the focal microinjection into the entopeduncular nucleus of the N-methyl-D-aspartate antagonist, 2-amino-7-phosphonoheptanoate (0.02 nmol) or the kainate antagonist, gamma-D-glutamylamino-methylsulphonate (40 nmol). Seizure threshold within the limbic system is modulated by excitatory systems controlling basal ganglia outputs. The relative importance of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor systems varies between different components of the basal ganglia.