ENHANCED NEUROPEPTIDE-Y RELEASE IN THE HIPPOCAMPUS IS ASSOCIATED WITHCHRONIC SEIZURE SUSCEPTIBILITY IN KAINIC ACID-TREATED RATS

We measured the release of neuropeptide Y (NPY) from hippocampal slice s of rats at various times after limbic seizures induced by a subcutan eous injection of 12 mg/kg kainic acid (KA). Two days after KA, 100 mM KCI induced a 1.6 +/- 0.2-fold increase in NPY release compared to sa line-injected rats (P < 0.05), while spontaneous and 50 mM KCl-induced release were unchanged. Thirty days after KA, the spontaneous and 100 mM KCl-induced efflux of NPY was enhanced 2-fold on average (P < 0.01 ) compared to controls, while no significant differences were found us ing 50 mM KCI. Tissue concentration of NPY was raised 2.2 +/- 0.2 time s (P < 0.01) 30 days after KA. Thirty days after KA, the rats showed e nhanced susceptibility to tonic-clonic seizures, assessed using a norm ally subconvulsive dose of pentylenetetrazol (PTZ; 30 mg/kg). A select ive antibody (Ab) raised against NPY in a rabbit was infused bilateral ly for three days in the CA3 area and dentate gyrus (DG) of the dorsal hippocampus of rats treated 30 days before with KA. This significantl y reduced (P < 0.05) the number of animals with tonic-clonic seizures induced by 30 mg/kg PTZ, compared to KA treated rats which received th e inactivated Ab. The Ab was ineffective in naive rats injected with a full convulsive dose of PTZ (55 mg/kg). The present results show that neuronal release of NPY is enhanced in the hippocampus after limbic s eizures induced in rats by KA. This effect persists for at least 30 da ys and may contribute to the chronically enhanced susceptibility to se izures after injection of this toxin.