THE EFFECTS OF ADENOSINE A(3) RECEPTOR STIMULATION ON SEIZURES IN MICE

We have previously shown that acute preischemic adenosine A(3) recepto r stimulation results in an increased postischemic damage, while chron ic stimulation of this receptor diminishes it. Since several pathophys iological phenomena are common for both ischemia and seizures, we have explored the effect of acute and chronic administration of the adenos ine A(3) receptor selective agonist IB-MECA (N-6-(3-iodobenzyl) adenos ine-5'-N-methylcarboxamide) prior to seizures induced by N-methyl-D-as partate (NMDA), pentamethylenetetrazole, or electric shock. At 100 mu g/kg, acutely injected IB-MECA was protective in chemically but not el ectrically induced seizures. In chronic administration of IB-MECA, sig nificant protection against chemically induced seizures was obtained i n all studied measures, i.e., seizure latency, neurological impairment , and survival. Although threshold voltage was unchanged in electrical ly induced seizures, a chronic regimen of IB-MECA significantly reduce d postepileptic mortality. Since the combination of an arteriole-const ricting compound 48/80 and hypotension-inducing clonidine injected pri or to NMDA results in a significant protection against seizures, and s ince acute stimulation of adenosine A(3) receptor causes both arteriol ar constriction and severe hypotension, there is a possibility that th e protection obtained by the acutely administered drug may result from inadequate delivery of chemoconvulsants to the brain. It is, however, unknown whether the protective effect of chronically administered IB- MECA is related to the effect of the drug on blood flow, neuronal mech anisms, or both.