SUBSTANTIA NIGRA-MEDIATED ANTICONVULSANT ACTION - A POSSIBLE ROLE OF A DOPAMINERGIC COMPONENT

A number of neural pathways may mediate nigral control of epilepsy. According to the literature, a GABAergic nigrotectal pathway may be responsible for the control exerted by the substantia nigra on the diffusion of discharges toward spinal targets, while the nigrothalamic Projection may transfer nigral influence on premotor neocortical epilepsy. Since there is probably an anatomical nigrohippocampal pathway arising from dopaminergic cells in the substantia nigra, we tested the effects of stimulating the substantia nigra pars compacta (SNpc) on focal hippocampal epilepsy induced by penicillin injection in the cat. The possibility of dopamine involvement was further tested by studying the effects of intraperitoneal injection of haloperidol, a dopamine receptor blocking agent on nigrohippocampal influences, while to verify the precise site of action, in other groups of cats, sulpiride and apomorphine (D-receptor antagonist and agonist, respectively) were locally administered in the dorsal hippocampus. Furthermore, modifications of hippocampal epileptiform EEG were studied in control conditions and following SNpc electrolytic lesions. Results showed a strong nigral suppressive effect on focal hippocampal epilepsy. Nigral stimulation induced a significant decrease in both frequency and amplitude of hippocampal spikes, which disappeared either about 10 min after i.p. injection of haloperidol 1 mg/kg or about 5 min after intrahippocampal administration of sulpiride, and did not return during a further hour or more of experimental observation. It should be emphasized that in the absence of nigral stimulatiion, both haloperidol and sulpiride dis not modify hippocampal spike frequency. Apomorphine application to dorsal hippocampus induced a marked reduction of hippocampal epileptiform activity parallel to the effect observed during SNpc stimulation. On the other hand, in SNpc-lesioned cats a certain degree of spiking enhancement was observed in hippocampal recordings. The experimental findings are regarded as evidence that the SNpc is able to control hippocampal-based epileptiform spikes and that this influence is dopaminergic in nature. The substantia nigra thus appears to have multiple elective influences, in different brain loci, on epileptic phenomena by selective activation of its different efferent projections, involving both GABAergic and dopaminergic systems. © 1990.