Catecholaminergic systems and amygdala kindling development. Effects of bilateral lesions of substantia nigra dopaminergic or locus coeruleus noradrenergic neurones

Abstract The effects of the bilateral and selective destruction of substantia nigra (SN) dopaminergic or locus coeruleus (LC) noradrenergic neurones, consecutive to a local injection of 6-hydroxydopamine, were studied on the development of amygdala kindling. Immunohistochemical controls of lesions were performed using selective dopamine (DA) or norepinephrine (NE) antibodies. The results demonstrated that a massive destruction of SN pars compacta neurones did not modify the rate of kindling development. Conversely, the lesions of LC neurones (sparing lateral tegmental nuclei) markedly facilitated the development of amygdala kindling. This effect was related to the extent of NE denervation. Together, these results suggest that DA is not strongly involved in the development of kindling, and the nigrostriatal output does not play a major role in the generalization of kindled seizures. In contrast, they confirm an inhibitory influence exerted by LC noradrenergic ascending pathways on the development of kindling.