Enhanced neuropeptide Y release in the hippocampus is associated with chronic seizure susceptibility in kainic acid treated rats.

We measured the release of neuropeptide Y (NPY) from hippocampal slices of rats at various times after limbic seizures induced by a subcutaneous injection of 12 mg/kg kainic acid (KA). Two days after KA, 100 mM KCl induced a 1.6 +/- 0.2-fold increase in NPY release compared to saline-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 using 50 mM KCl. Tissue concentration of NPY was raised 2.2 +/- 0.2 times (P < 0.01) 30 days after KA. Thirty days after KA, the rats showed enhanced susceptibility to tonic-clonic seizures, assessed using a normally subconvulsive dose of pentylenetetrazol (PTZ; 30 mg/kg). A selective antibody (Ab) raised against NPY in a rabbit was infused bilaterally for three days in the CA3 area and dentate gyrus (DG) of the dorsal hippocampus of rats treated 30 days before with KA. This significantly 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 the 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 seizures induced in rats by KA. This effect persists for at least 30 days and may contribute to the chronically enhanced susceptibility to seizures after injection of this toxin.