Inhibition of the substantia nigra suppresses absences and clonic seizuresin audiogenic rats, but not tonic seizures: Evidence for seizure specificity of the nigral control

GABAergic inhibition of the substantia nigra pars reticulata has been shown to suppress seizures in most models of epilepsy involving forebrain networ ks, such as absences or clonic seizures. No such antiepileptic effects were observed, however, in genetically audiogenic rats exhibiting tonic seizure s generated in the brainstem. This suggests a constitutive dysfunction of t he 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 th e substantia nigra had no effect in Wistar rats with audiogenic seizures (W istar AS). [H-3]Muscimol autoradiography suggested a 40% reduced density of GABAA receptors in the substantia nigra of Wistar AS, whereas no change wa s observed in the cortex and the superior colliculus (superficial and inter mediate layers), as compared to control animals. In Wistar AS where 40 repe titions of audiogenic stimulations progressively induced generalised convul sive seizures with both tonic and clonic components, bilateral injection of muscimol (350 pmol/side) in the substantia nigra suppressed the clonic com ponent but had no effect on tonic seizures. In hybrid rats issued from cros s-breeding between Wistar AS and rats with spontaneous absence seizures, bi lateral injection of muscimol (18 pmol/side) in the substantia nigra abolis hed cortical spike-and-wave discharges, but had no effect on tonic audiogen ic seizures at doses up to 700 pmol/side. These results show that despite a decreased number of GABAA receptors in th e substantia nigra, inhibition of this structure in Wistar AS still leads t o inhibition of seizures involving forebrain structures. These results conf irm that GABAergic inhibition of the substantia nigra has antiepileptic eff ects through the control of forebrain circuits. They suggest that this cont rol mechanism has no inhibitory effect on circuits underlying audiogenic to nic seizures. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.