GABAergic inhibition of the substantia nigra pars reticulata has been shown to suppress
seizures in most models of
epilepsy involving forebrain networks, such as absences or
clonic seizures. No such
antiepileptic effects were observed, however, in genetically audiogenic rats exhibiting
tonic seizures generated in the brainstem. This suggests a constitutive dysfunction of the nigral GABAergic neurotransmission in this strain of rat or a selective action of the nigral control on specific networks. In the present study, we first confirmed that bilateral injection of
muscimol (700 pmol/side) in the substantia nigra had no effect in Wistar rats with audiogenic
seizures (Wistar AS). [3H]
Muscimol autoradiography suggested a 40% reduced density of
GABA(A) receptors in the substantia nigra of Wistar AS, whereas no change was observed in the cortex and the superior colliculus (superficial and intermediate layers), as compared to control animals. In Wistar AS where 40 repetitions of audiogenic stimulations progressively induced generalised convulsive
seizures with both tonic and clonic components, bilateral injection of
muscimol (350 pmol/side) in the substantia nigra suppressed the clonic component but had no effect on
tonic seizures. In hybrid rats issued from cross-breeding between Wistar AS and rats with spontaneous absence
seizures, bilateral injection of
muscimol (18 pmol/side) in the substantia nigra abolished cortical spike-and-wave discharges, but had no effect on tonic audiogenic
seizures at doses up to 700 pmol/side. These results show that despite a decreased number of
GABA(A) receptors in the substantia nigra, inhibition of this structure in Wistar AS still leads to inhibition of
seizures involving forebrain structures. These results confirm that GABAergic inhibition of the substantia nigra has
antiepileptic effects through the control of forebrain circuits. They suggest that this control mechanism has no inhibitory effect on circuits underlying audiogenic
tonic seizures.