Seizure suppression in kindling epilepsy by intrahippocampal locus coeruleus grafts: evidence for an alpha-2-adrenoreceptor mediated mechanism

Summary Intrahippocampal cell suspension grafts, prepared from the locus coeruleus region of rat fetuses, have previously been shown to retard seizure development in rats made hypersensitive to hippocampal kindling by a lesion of the forebrain noradrenergic system. The objective of the present study was to provide evidence that the seizure-suppressant effect elicited by the grafts is mediated via noradrenergic mechanisms. Two groups of rats received 6-hydroxydopamine in the lateral ventricle and then bilateral intrahippocampal locus coeruleus grafts. After 3 months, the grafted animals and a group of normal rats were subjected to hippocampal kindling. One group of grafted animals and the normal rats were injected intraperitoneally with the alpha-2 adrenergic receptor blocker idazoxan before each kindling stimulation. The other grafted rats received vehicle injections. The development of seizures was significantly faster in the grafted and normal rats that had been given idazoxan than in the grafted rats that had not been subjected to alpha-2 receptor blockade. Our data suggest that the seizure-suppressant action exerted by grafts of fetal locus coeruleus in hippocampal kindling is mediated via noradrenergic mechanisms, most likely via activation of postsynaptic alpha-2 adrenoreceptors.     

Ventrolateral medullary pressor area: site of hypotensive action of clonidine

Intravenous injections of clonidine produce an initial transient increase in blood pressure followed by a long-lasting hypotension and bradycardia. The initial pressor response is due to activation of vascular alpha 1-adrenergic receptors while the hypotension and bradycardia are caused by the central actions of clonidine. Although, hypothalamus, nucleus tractus solitarius (NTS), ventrolateral medulla and the intermediolateral cell column of the thoracolumbar spinal cord (IML) have been implicated, the exact site of these actions of clonidine in the central nervous system is not established. The results of this investigation suggest that the pressor area in the ventrolateral medulla (VLPA) is the site of hypotensive and bradycardic actions of intravenously administered clonidine. This conclusion is based on the observation that microinjections of idazoxan, a specific alpha 2-adrenergic receptor blocker, into the VLPA prevented and reversed the hypotension and bradycardia despite the fact that other proposed sites of these actions (NTS, hypothalamus and IML) were intact and accessible to intravenously administered clonidine.