Alterations of noradrenaline and serotonin uptake and metabolism in chronic cobalt-induced epilepsy in the rat.
The high affinity uptake of noradrenaline and serotonin, and the concentrations of these monoamines and their metabolites, have been measured in the perifocal cortical area at various stages of the evolution of cobalt-induced epilepsy in the rat. Noradrenaline uptake was maximally reduced at days 8-10 after cortical cobalt application, a time corresponding to the onset of epileptic discharges; it remained diminished during the spiking activity period of the focus (days 14-20) and was back to normal values at day 40, at which time the epileptic syndrome had disappeared. Serotonin uptake was also diminished at days 8-10 but to a lesser extent than was noradrenaline uptake. In the homotopic cerebral cortex contralateral to cobalt application, noradrenaline uptake was reduced at day 10 only and to a lesser extent than in the perifocal area, whereas serotonin uptake was unaffected. Kinetic analysis of the cobalt-induced monoamine uptake alterations at day 10 revealed a diminution of the maximal velocity with no change in the Km. Noradrenaline and dihydroxyphenylethyleneglycol concentrations in the perifocal area were also maximally reduced at days 8-10 but were unaffected at day 2 and day 40 post cobalt application. A reduction of serotonin levels in the perifocal area was observed only at days 8-10 while 5-hydroxyindoleacetic acid remained unaffected throughout the time period studied. The levels of these monoamines and their metabolites were unchanged in the homotopic contralateral cortex 2-40 days after cobalt application. These results indicate that cortical cobalt application induces alterations of the biochemical indices of the density of noradrenaline-containing terminals that closely parallel the evolution of the epileptic syndrome. These data further emphasize the important role of the cortical noradrenergic system in cobalt-induced epilepsy.
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003035:Cobalt; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007700:Kinetics; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000032:analysis; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D003035:Cobalt; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine