Lesions of noradrenergic neurons in rats with spontaneous generalized non-convulsive epilepsy

The role of noradrenergic neurons in the control of a spontaneous generalized non-convulsive epilepsy (GNCE) was investigated. In rats with genetic spontaneous absence seizures, we produced lesions using 2 neurotoxins: 6-hydroxydopamine (6-OHDA) and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). Lesions of noradrenergic neurons were made either in pups by neonatal 6-OHDA intraperitoneal (i.p.) injection (2 x 100 mg/kg) or in adult rats by i.p. administration of DSP4 (60 mg/kg) or bilateral microinjection of 6-OHDA in the locus coeruleus (LC) (4 micrograms/microliters, 2 microliters/side). Effectiveness of the lesions was controlled by measuring dopamine (DA) and noradrenaline (NA) contents in the brains. Neonatal 6-OHDA administration did not lead to any difference in seizures in adult animals, compared with control rats. DSP4 injections and LC lesions with local injections of 6-OHDA produced a transient increase of the seizures. Within one to two weeks, the seizure duration went back to prelesion levels. No seizure occurred when the same lesions were performed in non epileptic rats. These results suggest that NA is not involved in the genesis of this generalized non-convulsive epilepsy; they confirm that NA participates in the control of seizures in this model, but the rapid development of compensatory mechanisms shows that this control is not critical.