Studies on the cyclic AMP-generating system of cerebral cortex with iron-induced epileptic focus

The cyclic AMP contents of cortical slices after incubation with or without agents such as norepinephrine were determined in four areas of rat cerebral cortex in which FeCl(2) solution was injected into the unilateral sensorimotor cortex to induce an epileptic focus. Norepinephrine, isoproterenol and phenylephrine elevated the cyclic AMP levels of cortical slices 4- to 7-fold, 2- to 4-fold and 1.5- to 3-fold, respectively. The elicitation of cyclic AMP accumulation by norepinephrine was inhibited by 30 to 60% with phentolamine and 65 to 80% with propranolol. 8-Phenyltheophylline almost completely inhibited the elicitation of cyclic AMP accumulation by a norepinephrine-propranolol combination but not by a norepinephrine-phentolamine combination. In anterior cortical areas of rats in which the appearance of isolated spikes in electrocorticograms was dominant either ipsilaterally or contralaterally to the injection site 8 to 10 days after the injection of FeCl(2) solution, the elevated levels of cyclic AMP elicited by norepinephrine, isoproterenol and a norepinephrine-phentolamine combination were higher on the side of dominant spike activity than on the other. In anterior cortical areas of rats showing dominant spike activity on either side of the cortex 31 to 60 days after the injection, the elevated levels of cyclic AMP elicited by norepinephrine and phenylephrine were lower on the dominant side than on the other. In anterior cortical areas of rats showing nearly equal spike activity on the two sides 31 to 60 days after the injection, the elevated levels of cyclic AMP elicited by norepinephrine, isoproterenol and a norepinephrine-phentolamine combination were higher on the side ipsilateral to the injection site than on the other. In these rats, a similar regional difference in the norepinephrine-elicited accumulation of cyclic AMP was detected 19 to 21 days after the injection. In anterior and posterior cortical areas of rats in which the appearance of spike and slow wave complexes as well as isolated spikes were detected 31 to 60 days after the injection, the elevated levels of cyclic AMP elicited by norepinephrine, isoproterenol, phenylephrine and combinations of norepinephrine and phentolamine or propranolol were higher on the side ipsilateral to the injection site than on the other. The tendency for the norepinephrine-elicited accumulation of cyclic AMP to be related to the epileptic discharge patterns in rats 61 to 90 days after the injection was similar to that in rats 31 to 60 days after the injection. The regional differences in cyclic AMP contents of incubated cortical slices are discussed with regard to the neurochemical process of iron-induced epilepsy.