Seizure suppression in kindling epilepsy by intrahippocampal locus coeruleus grafts: evidence for an alpha-2-adrenoreceptor mediated mechanism.
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.
Bengzon
J
J
Department of Medical Cell Research, University of Lund, Sweden.
Kokaia
M
M
Brundin
P
P
Lindvall
O
O
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000032:analysis; D004827:Epilepsy / Q000503:physiopathology / Q000601:surgery*; D006624:Hippocampus / Q000502:physiology* / Q000503:physiopathology; D006892:Hydroxydopamines; D019329:Idazoxan; D007696:Kindling, Neurologic / Q000187:drug effects; D008125:Locus Coeruleus / Q000637:transplantation*; D008297:Male; D009474:Neurons / Q000201:enzymology / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012640:Seizures / Q000503:physiopathology / Q000601:surgery*; D016042:Transplantation, Heterotopic
D000319:Adrenergic beta-Antagonists; D004146:Dioxanes; D006892:Hydroxydopamines; D011942:Receptors, Adrenergic, alpha; D016627:Oxidopamine; D004299:Dopamine beta-Hydroxylase; D019329:Idazoxan