ELECTRICAL KINDLING OF THE HIPPOCAMPUS IS ASSOCIATED WITH FUNCTIONAL ACTIVATION OF NEUROPEPTIDE Y-CONTAINING NEURONS

The release of neuropeptide Y (NPY) was measured from hippocampal slices of rats at stage 2 (preconvulsive stage) and stage 5 (full seizure expression) of electrical kindling of the dorsal hippocampus (upper blade of the dentate gyrus). Spontaneous release in naive rats (9.0+/-0.8 fmol/ml every 10 min) was independent of external Ca2+ but was reduced by 38+/-3.6% (P < 0.05) during 20 min incubation with 5 muM tetrodotoxin. Spontaneous efflux in naive rats did not differ from that in shams (implanted with electrodes but not stimulated) or in rats kindled to stage 2 and stage 5. Twenty-five, 50 and 100 mM KCl induced a concentration-dependent release of NPY (P < 0.05 and P < 0.01 at 25 and 50 - 100 mM respectively) from slices of shams. The effect of 100 mM KCl was reduced by 94+/-1% (P < 0.01) in the absence of Ca2+. Two days after the last stage 2 stimulation and 1 week after the last stage 5 seizure, NPY release was significantly larger than in shams at all KCl concentrations in the stimulated and contralateral hippocampus (P < 0.05 and P < 0.01). Forty-eight hours after one single after-discharge and 1 month after the last stage 5 seizure, 50 mM KCl induced a significantly larger release of NPY in the stimulated and contralateral hippocampus (P < 0.01 and P < 0.05), although the effect was less than during kindling. The tissue concentration of NPY increased significantly in both hippocampi at stage 2 and 1 week after stage 5 (2.6 times on average, P < 0.01) but no significant differences were found 1 month after stage 5. The present results provide the first evidence of enhanced neuronal release of NPY during kindling, suggesting that this neuropeptide may have a potential role in epileptogenesis.